efsa report

EFSA Journal 2012;10(8):2860

Suggested citation: European Food Safety Authority; Conclusion on the peer review of the pesticide risk assessment of the

active substance penflufen. EFSA Journal 2012;10(8):2860. [74 pp.] doi:10.2903/j.efsa.2012.2860. Available online:

www.efsa.europa.eu/efsajournal

© European Food Safety Authority, 2012

CONCLUSION ON PESTICIDE PEER REVIEW

Conclusion on the peer review of the pesticide risk assessment of the active

substance penflufen1

European Food Safety Authority2

European Food Safety Authority (EFSA), Parma, Italy

ABSTRACT

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk

assessments carried out by the competent authority of the rapporteur Member State the United Kingdom, for the

pesticide active substance penflufen are reported. The context of the peer review was that required by

Commission Regulation (EU) No 188/2011. The conclusions were reached on the basis of the evaluation of the

representative use of penflufen as a fungicide on potatoes. The reliable endpoints concluded as being appropriate

for use in regulatory risk assessment, derived from the available studies and literature in the dossier peer

reviewed, are presented. Missing information identified as being required by the regulatory framework is listed.

Concerns are identified.

© European Food Safety Authority, 2012

KEY WORDS

Penflufen, peer review, risk assessment, pesticide, fungicide

1 On request from the European Commission, Question No EFSA-Q-2011-01197, approved on 27 July 2012.

2 Correspondence: [email protected]

mailto:[email protected]

Peer review of the pesticide risk assessment of the active substance penflufen

EFSA Journal 2012;10(8):2860 2

SUMMARY

Penflufen is a new active substance for which in accordance with Article 6(2) of Council Directive

91/414/EEC the United Kingdom (hereinafter referred to as the „RMS‟) received an application from

Bayer CropScience AG for approval. Complying with Article 6(3) of Directive 91/414/EEC, the

completeness of the dossier was checked by the RMS. The European Commission recognised in

principle the completeness of the dossier by Commission Decision 2010/672/EU of 5 November 2010.

The RMS provided its initial evaluation of the dossier on penflufen in the Draft Assessment Report

(DAR), which was received by the EFSA on 4 August 2011. The peer review was initiated on 12

September 2011 by dispatching the DAR for consultation of the Member States and the applicant

Bayer CropScience AG.

Following consideration of the comments received on the DAR, it was concluded that EFSA should

conduct an expert consultation in the areas of mammalian toxicology and ecotoxicology and EFSA

should adopt a conclusion on whether penflufen can be expected to meet the conditions provided for in

Article 5 of Directive 91/414/EEC, in accordance with Article 8 of Commission Regulation (EU) No

188/2011.

The conclusions laid down in this report were reached on the basis of the evaluation of the

representative uses of penflufen as a fungicide on potatoes, as proposed by the applicant. Full details

of the representative uses can be found in Appendix A to this report.

In the area of identity, physical/chemical/technical properties and methods of analysis one data gap

was identified for a method of analysis for the metabolite M01 in groundwater.

In the mammalian toxicology chapter one data gap was identified on the toxicological relevance of

impurities present in the technical specification. No critical areas of concern were identified.

EFSA was unable to conclude whether a specific residue definition is needed for the rotational crops

and a data gap was set to provide rotational crop field trials on cereals, leafy vegetables, root

vegetables and soybean at a dose rate covering the calculated plateau concentration of penflufen in soil

in order to determine the residue levels of penflufen and metabolites M01 (free and conjugated), M49,

M58, M63, M64 and M65.The consumer risk assessment could not be concluded on.

Isomers of penflufen and its metabolite M01 have not been separately analysed in any of the studies

performed to investigate the fate and behaviour of penflufen in the environment and potential

enantioselective transformation is not addressed by the available data. Due to the lack of a soil

photolysis study, available data permit only to assess uses with immediate incorporation and no direct

exposure of the active substance to sunlight. Potential groundwater contamination was assessed for the

use in seed potatoes planted only once every three years. The limit of 0.1 µg/l was exceeded for 1 of 9

scenarios when the PEARL model was used. The limit of 0.1 µg/l was exceeded by metabolite M01 in

all 9 scenarios when simulated with PEARL and the accepted default uptake factor of 0. A critical area

of concern was identified for potential groundwater contamination by metabolite M01. In this case the

level of 0.75 µg/l was exceeded in 7 of the 9 scenarios. Metabolite M02 did not exceed the limit of 0.1

µg/l for any of the scenarios simulated.

Based on the available information a low risk to non-target organisms was concluded for penflufen

used as a seed treatment on potato, with the exception of the long-term risk to birds. A data gap for a

further assessment of the long-term risk to birds was therefore identified.


EFSA Journal 2012;10(8):2860 3

TABLE OF CONTENTS

Abstract .................................................................................................................................................... 1 Summary .................................................................................................................................................. 2 Table of contents ...................................................................................................................................... 3 Background .............................................................................................................................................. 4 The active substance and the formulated product .................................................................................... 6 Conclusions of the evaluation .................................................................................................................. 6 1. Identity, physical/chemical/technical properties and methods of analysis ...................................... 6 2. Mammalian toxicity ......................................................................................................................... 6 3. Residues ........................................................................................................................................... 8 4. Environmental fate and behaviour ................................................................................................... 8 5. Ecotoxicology .................................................................................................................................. 9 6. Overview of the risk assessment of compounds listed in residue definitions triggering assessment

of effects data for the environmental compartments .............................................................................. 13 6.1. Soil ........................................................................................................................................ 13 6.2. Ground water ........................................................................................................................ 13 6.3. Surface water and sediment .................................................................................................. 14 6.4. Air ......................................................................................................................................... 14

7. List of studies to be generated, still ongoing or available but not peer reviewed .......................... 16 8. Particular conditions proposed to be taken into account to manage the risk(s) identified ............. 16 9. Concerns ........................................................................................................................................ 16

9.1. Issues that could not be finalised .......................................................................................... 16 9.2. Critical areas of concern ....................................................................................................... 17 9.3. Overview of the concerns identified for each representative use considered ....................... 18

References .............................................................................................................................................. 19 Appendices ............................................................................................................................................. 21 Abbreviations ......................................................................................................................................... 71


EFSA Journal 2012;10(8):2860 4

BACKGROUND

In accordance with Article 80(1)(a) of Regulation (EC) No 1107/20093, Council Directive

91/414/EEC4 continues to apply with respect to the procedure and conditions for approval for active

substances for which a decision recognising in principle the completeness of the dossier was adopted

in accordance with Article 6(3) of that Directive before 14 June 2011.

Commission Regulation (EU) No 188/20115 (hereinafter referred to as „the Regulation‟) lays down the

detailed rules for the implementation of Council Directive 91/414/EEC as regards the procedure for

the assessment of active substances which were not on the market on 26 July 1993. This regulates for

the European Food Safety Authority (EFSA) the procedure for organising the consultation of Member

States and the applicant for comments on the initial evaluation in the Draft Assessment Report (DAR)

provided by the rapporteur Member State (RMS), and the organisation of an expert consultation,

where appropriate.

In accordance with Article 8 of the Regulation, EFSA is required to adopt a conclusion on whether the

active substance is expected to meet the conditions provided for in Article 5 of Directive 91/414/EEC

within 4 months from the end of the period provided for the submission of written comments, subject

to an extension of 2 months where an expert consultation is necessary, and a further extension of upto

8 months where additional information is required to be submitted by the applicant in accordance with

Article 8(3).

In accordance with Article 6(2) of Council Directive 91/414/EEC the United Kingdom (hereinafter

referred to as the „RMS‟) received an application from Bayer CropScience AG for approval of the

active substance penflufen. Complying with Article 6(3) of Directive 91/414/EEC, the completeness

of the dossier was checked by the RMS. The European Commission recognised in principle the

completeness of the dossier by Commission Decision 2010/672/EU6.

The RMS provided its initial evaluation of the dossier on penflufen in the DAR, which was received

by the EFSA on 4 August 2011 (United Kingdom, 2011). The peer review was initiated on 12

September 2011 by dispatching the DAR to Member States and the applicant Bayer CropScience AG

for consultation and comments. In addition, the EFSA conducted a public consultation on the DAR.

The comments received were collated by the EFSA and forwarded to the RMS for compilation and

evaluation in the format of a Reporting Table. The applicant was invited to respond to the comments

in column 3 of the Reporting Table. The comments and the applicant‟s response were evaluated by the

RMS in column 3.

The need for expert consultation and the necessity for additional information to be submitted by the

applicant in accordance with Article 8(3) of the Regulation were considered in a telephone conference

between the EFSA, the RMS, and the European Commission on 13 January 2012. On the basis of the

comments received, the applicant‟s response to the comments and the RMS‟s evaluation thereof it was

concluded that additional information should be requested from the applicant and the EFSA should

organise an expert consultation in the areas of mammalian toxicology and ecotoxicology.

3 Regulation (EC) No 1107/2009 of the European Parliament and of the Council of 21 October 2009 concerning the placing

of plant protection products on the market and repealing Council Directives 79/117/EEC and 91/414/EEC. OJ No L 309,

24.11.2009, p. 1-50. 4 Council Directive 91/414/EEC of 15 July 1991 concerning the placing of plant protection products on the market. OJ L 230,

19.8.1991, p. 1-32, as last amended. 5 Commission Regulation (EU) No 188/2011 of 25 February 2011 laying down detailed rules for the implementation of

Council Directive 91/414/EEC as regards the procedure for the assessment of active substances which were not on the market

2 years after the date of notification of that Directive. OJ No L 53, 26.2.2011, p. 51-55. 6 Commission Decision 2010/672/EU of 5 November 2010 recognising the completeness of the dossiers submitted for

detailed examination in view of the possible inclusion of penflufen and fluxapyroxad in Annex I to Council Directive

91/414/EEC. OJ No L 290, 6.11.2010, p. 51-52.


EFSA Journal 2012;10(8):2860 5

The outcome of the telephone conference, together with EFSA‟s further consideration of the

comments is reflected in the conclusions set out in column 4 of the Reporting Table. All points that

were identified as unresolved at the end of the comment evaluation phase and which required further

consideration, including those issues to be considered in an expert consultation, and the additional

information to be submitted by the applicant, were compiled by the EFSA in the format of an

Evaluation Table.

The conclusions arising from the consideration by the EFSA, and as appropriate by the RMS, of the

points identified in the Evaluation Table, together with the outcome of the expert consultation where

this took place, were reported in the final column of the Evaluation Table.

A final consultation on the conclusions arising from the peer review of the risk assessment took place

with Member States via a written procedure in July 2012.

This conclusion report summarises the outcome of the peer review of the risk assessment on the active

substance and the representative formulation evaluated on the basis of the representative uses as a

fungicide on potatoes, as proposed by the applicant. A list of the relevant end points for the active

substance as well as the formulation is provided in Appendix A. In addition, a key supporting

document to this conclusion is the Peer Review Report, which is a compilation of the documentation

developed to evaluate and address all issues raised in the peer review, from the initial commenting

phase to the conclusion. The Peer Review Report (EFSA, 2012) comprises the following documents,

in which all views expressed during the course of the peer review, including minority views, can be

found:

• the comments received on the DAR,

• the Reporting Table (16 January 2012),

• the Evaluation Table (24 July 2012),

• the reports of the scientific consultation with Member State experts

• the comments received on the assessment of the additional information (where relevant),

• the comments received on the draft EFSA conclusion.

Given the importance of the DAR including its addendum (compiled version of May 2012 containing

all individually submitted addenda (United Kingdom, 2012)) and the Peer Review Report, both

documents are considered respectively as background documents A and B to this conclusion.


EFSA Journal 2012;10(8):2860 6

THE ACTIVE SUBSTANCE AND THE FORMULATED PRODUCT

Penflufen is the ISO common name for 2′-[(RS)-1,3-dimethylbutyl]-5-fluoro-1,3-dimethylpyrazole-4-

carboxanilide (IUPAC).

The representative formulated product for the evaluation was „BYF 14182 FS 050‟ a flowable

concentrate for seed treatment (FS) containing 50 g/l penflufen.

The representative uses evaluated comprise of an indoor tuber treatment before planting or outdoor on-

planter spray at planting. Full details of the GAP can be found in the list of end points in Appendix A.

CONCLUSIONS OF THE EVALUATION

It must be noted that penflufen is a racemate, but the possible preferential metabolism/degradation of

each enantiomer in animals, plants and the environment was not investigated in the studies submitted

in the dossier and was therefore not considered during the peer review. Moreover, the analytical

methods used in the studies reported through all sections were not stereo-selective, and all values

mentioned as „penflufen‟ have to be considered as sum of isomers.

1. Identity, physical/chemical/technical properties and methods of analysis

The following guidance documents were followed in the production of this conclusion:

SANCO/3030/99 rev.4 (European Commission, 2000) and SANCO/825/00 rev. 8.1 (European

Commission, 2004).

The minimum purity of the active substance as manufactured is 950 g/kg, which is based on pilot plant

production. There is no FAO specification for penflufen.

The main data regarding the identity of penflufen and its physical and chemical properties are given in

Appendix A.

Penflufen (sum of isomers) is the residue definition for plants, soil, surface water and air. Products of

plant origin were analysed by LC-MS/MS and the method is validated for dry, wet and acidic

matrices. The validation for oily matrices was not acceptable. Data were available on the extraction

efficiency of this method. A method for products of animal origin is not necessary as no MRLs are

proposed. LC-MS/MS methods are available for soil, water and air. However, as the metabolite M01

is included in the residue definition for groundwater, a data gap is identified for a method of analysis.

A method for body fluids and tissues is not required as the active substance is not classified as toxic or

very toxic.

2. Mammalian toxicity

The following guidance document was followed in the production of this conclusion: European

Commission, 2003.

Penflufen was discussed during the Pesticides Peer Review expert meeting in May 2012 (PPR 90).

The technical material tested in the mammalian toxicology studies was considered representative of

the proposed specification; however based on the available information it was not possible to conclude

on the relevance of the impurities present in the proposed specification (a data gap was identified).

Penflufen is rapidly and extensively absorbed after oral administration; it is extensively metabolised

and rapidly and extensively excreted (within 3 days after exposure). It is neither acutely toxic after

oral, inhalatory and dermal exposure, nor a skin and eye irritant, nor a sensitiser.

Main target organs are the liver (diffuse centrilobular hepatocellular hypertrophy and increased organ

weight) and thyroid (diffuse follicular cell hypertrophy, sometimes accompanied by focal/multifocal


EFSA Journal 2012;10(8):2860 7

colloid) after both short and long-term repeated exposures (the relevant NOAELs are 7.7 mg/kg bw

per day (1 year study in dogs) and 4 mg/kg bw per day (2 year study in rats), respectively). The

classification as Carcinogenic, Carc cat 2 (according to GHS) was proposed during the meeting based

on the presence of liver adenomas in female rats, ovary tubulostromal adenomas in rats, histiocytic

sarcoma in male rats, brain astrocytomas in male rats and liver carcinomas in male and female mice7.

The relevant NOAEL for carcinogenicity is 79 mg/kg bw per day.

Penflufen is not a reproductive toxicant: the relevant parental, offspring and reproductive NOAELs are

58 mg/kg bw per day (the delayed vaginal opening occurring in the study was considered treatment-

related and could not be explained entirely by a decreased body weight in pups. However, this change

alone was not considered sufficient to trigger a proposal for classification for reproductive toxicity).

Penflufen is not a developmental toxicant, with the relevant maternal and developmental NOAELs of

100 and 300 mg/kg bw per day, respectively. Penflufen did not show any evidence of neurotoxicity.

The Acceptable Daily Intake (ADI) is 0.04 mg/kg bw per day based on the NOAEL from the 2-year

rat study, applying an uncertainty factor of 100. The Acute Reference Dose (ARfD) is 0.5 mg/kg bw

based on the rat acute neurotoxicity study, applying an uncertainty factor of 100. The Acceptable

Operator Exposure Level (AOEL) is 0.077 mg/kg bw per day based on the 1-year dog study, with an

uncertainty factor of 100.

During the meeting, the toxicological relevance of plant metabolite M63 was discussed. No

toxicological data were available for the metabolite M63, which is structurally similar to M61, a minor

rat metabolite. This would suggest that the plant metabolism is not significantly different from the rat

metabolism; however, based on the available data, the experts could not reliably conclude if the

reference values of penflufen are applicable to the metabolite M63 as well. The same applies to

metabolites M49, M58, M64 and M65, for which a concern might be raised in rotational crops (further

toxicological data might be needed based on the results of the residue trials).

Metabolite M01, on the basis of FOCUS groundwater modelling, has the potential to contaminate

groundwater (exceeding the triggers of 0.1 µg/L and 0.75 µg/L in the majority of the scenarios). It is

an intermediate in the rat metabolism, and available data indicate that it does not possess genotoxic

potential. However, based on the classification of penflufen as Carcinogenic, Carc cat 2 (according to

GHS) discussed during the meeting, M01 should be considered a relevant metabolite for groundwater,

unless the contrary is proven and subject to the final decision in EChA. M01 is also a plant metabolite.

Treatments with „BYF 14182 FS 050‟ can be done before planting by roller table or at planting

directly in the furrow. The exposure estimate for operators is 17% of the AOEL for the in furrow

method with no PPE and 10% of the AOEL for the roller table method (with the use of coveralls and

protective gloves when handling the concentrate, contaminated surfaces and freshly treated materials).

The re-entry worker exposure (using manual planters when planting treated potatoes) is 48% of the

AOEL. The impact of each individual enantiomer on the toxicity, relevant for the re-entry activities,

was not assessed. However, considering the worst case that only one enantiomer is responsible for the

recorded toxicity, would lead to an exposure of 96% of the AOEL, which could be further reduced

with the use of gloves. Bystander exposure is considered negligible.

7 It should be noted that classification is formally proposed and decided in accordance with Regulation (EC) No 1272/2008

(Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification,

labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and

amending Regulation (EC) No 1907/2006. OJ No L 353, 31.12.2008. p. 1-1355). Proposals for classification made in the

context of the evaluation procedure under Regulation (EC) No 1107/2009 are not formal proposals.


EFSA Journal 2012;10(8):2860 8

3. Residues

The assessment in the residue section below is based on the guidance documents listed in the

document 1607/VI/97 rev.2 (European Commission, 1999), and the JMPR recommendations on

livestock burden calculations stated in the 2004 and 2007 JMPR reports (JMPR, 2004 and 2007).

The metabolism of penflufen was investigated in potatoes, wheat straw and soybean as a seed

treatment and after an in-furrow soil application in potatoes and paddy rice using both the pyrazole

and the phenyl 14

C labelling forms of penflufen. Penflufen and the metabolite M01 (free and

conjugated) were the predominant compounds of the total residues in potato tubers both after the seed

treatment (2.5N) (22% and 19% of TRR, respectively) and the in-furrow soil application (28% and

10%TRR, respectively) as well as in paddy rice grain after the in-furrow soil application (31% and

23% TRR, respectively). Since the total radioactive residues in wheat grain were very low (<0.01

mg/kg) no further metabolites characterization or identification was attempted. Penflufen was detected

neither in wheat straw nor in soybean seeds after a seed application. In wheat straw, the parent

compound was extensively metabolised mainly into metabolite M01 both in its free and conjugated

forms (5% and 50% TRR, respectively). The metabolic profile was seen to be different in soybean

seeds where penflufen and M01 were not detected and the total radioactive residues consisted mainly

of metabolite M63 (65% TRR) resulting from the cleavage of the parent compound at the carboxamide

linkage, along with metabolite M49 (up to 77% TRR).

Confined rotational crop studies (wheat, soybean and turnip) were conducted after a bare soil

treatment at a dose rate of 530 g a.s./ha and indicated that penflufen was intensively degraded and

detected only in wheat straw and turnip roots (3.2% and 15.6%, respectively). Besides the glucoside

conjugated M01 accounting for 53% to 85% TRR in wheat grain, soybean seeds and turnip roots, the

metabolic profile was dominated by the pyrazole derivated metabolites M58, M63, M64, M65

resulting from the cleavage of the parent molecule at the carboxamide bond, which accounted globally

for up to 57% TRR in wheat grain, 83% TRR in soybean seeds and 35% TRR in turnip roots. The

predominance of the pyrazole derivated metabolites in the rotational crop metabolism study when

compared to the primary crops is probably the result of the different application patterns. Treatment in

the confined rotational crop study was done to the bare soil without soil incorporation and it is

postulated that penflufen could be subject to a photolytic degradation resulting in the formation of the

pyrazole metabolites followed by plant uptake, however no soil photolysis study was available to

substantiate such a hypothesis.

Rotational crop field trials were conducted on carrot, lettuce and wheat/barley at an application rate of

100 g a.s./ha and were under dosed (0.2 N) considering the calculated plateau concentration in soil. It

was also noted that only free M01 was analysed since the analytical method did not contain a

hydrolysis step. Moreover, this study did not address the case of soybean in rotation where the

metabolism was seen to be different and where significant residues of M01 (free and conjugated),

M49, M63, M64 and M65 are expected. At this stage EFSA is unable to conclude whether a specific

residue definition is needed for rotational crops and a data gap was identified to provide rotational

crop field trials on cereals, leafy vegetables, root vegetables and soybean at a dose rate covering the

calculated plateau concentration of penflufen in soil in order to determine the residue levels of

penflufen and metabolites M01 (free and conjugated), M49, M58, M63, M64 and M65.

Penflufen was considered as a valid marker of the total residues in root and tuber vegetables, and the

residue definition for monitoring was limited to the parent compound only (sum of isomers). For risk

assessment, since metabolite M01 was recovered at comparable levels as the parent compound in

potato tubers after seed and in-furrow soil treatments, it was initially suggested to include this

metabolite in the residue definition for risk assessment. However, in the GAP complying residue trials

on potato, metabolite M01 was not detected and it is the opinion of EFSA not to include M01 and to

limit the residue definition for risk assessment to the parent penflufen (sum of isomers) for root and

tuber vegetables (seed and in-furrow soil treatments only).


EFSA Journal 2012;10(8):2860 9

Penflufen remained stable under hydrolytic conditions representative of pasteurisation, baking,

brewing, boiling and sterilisation and no study to address the magnitude of penflufen in processed

commodities was triggered.

A sufficient number of residue trials conducted on potatoes in Northern and Southern Europe were

provided and considered as acceptable to derive a MRL of 0.01*mg/kg. Since EFSA was unable to

conclude on the residue definition and the potential need for MRLs on rotational crops, no reliable

residue definition based on the available ruminant and poultry metabolism studies could be derived

and the setting of a robust residue definition should be considered pending the outcome of the

identified data gap on rotational crops. A consumer dietary risk assessment considering the proposed

MRL on potato and using the EFSA PRIMo model indicated a negligible chronic and acute intake for

all consumer groups (TMDI <1% ADI and IESTI <1% ARfD). This calculation has to be regarded as

provisional pending the final residue definition and the need for MRLs in rotational crops. Finally it

should be added that the potential preferential metabolism/degradation of each enantiomer of

penflufen in animals and plants was not investigated in the studies submitted in the dossier and was

therefore not considered during the peer review. Nevertheless, this has no impact on the consumer risk

assessment in view of the large margin of safety for the representative use. However, if in the future

additional uses are intended, the preferential metabolism/degradation of each enantiomer in plants and

animals as well as the possible impact on the consumer exposure assessment need to be reconsidered.

4. Environmental fate and behaviour

Isomers of penflufen and its metabolite M01 have not been separately analysed in any of the studies

performed to investigate the fate and behaviour of penflufen in the environment. Therefore, for those

processes in which microbial metabolisation is involved, some degree of enantioselective

transformation cannot be excluded. Considering that a sufficient margin of safety has been identified

in the environmental risk assessment for the representative uses evaluated, no further data in relation

to the potential enantioselective degradation of penflufen in the environment is needed to finalise the

EU risk assessment.

Degradation of penflufen in soil in the laboratory under aerobic conditions was investigated in four

European soils (20 °C) and two North American soils (25 °C). Penflufen exhibits high to very high

persistence under these conditions. Hydroxylation of penflufen yields major metabolite M01.

Formation and degradation rates of this metabolite have been derived from the data in the laboratory

studies. Due to the slow degradation of the parent the metabolite appears late in the experiments and

no significant degradation is observed. Calculated formation and degradation rates may be expected to

be heavily correlated. According to these calculations metabolite M01 may be considered to exhibit

moderate to very high persistence in soil. Subsequent transformation of this metabolite yields the

major metabolite M02. Mineralization in the six soils ranged between 1.5 % AR and 6.5 % AR at 20

°C (after 120 d) and between 7.9 % and 9.8 % AR at 25 °C (after 365 d). Non-extractable residues

were between 10.1 % AR and 19.3 % AR at 20 °C (after 120 d) and between 17.6 % and 25.8 % AR at

25 °C (after 365 d). Since data in the experiments performed with the parent compound do not allow

reliable degradation parameters for this metabolite to be derived, a study to investigate the degradation

of M02 under laboratory aerobic conditions was performed in four soils. M02 may be considered to

exhibit high persistence in soil (FOCUS, 2006).

Field studies are available at six European locations. In these studies, penflufen was incorporated

immediately after application and grass was planted on the sites in order to simulate the conditions

prevailing for the representative use proposed. Normalised DT50 values were calculated for the parent

compound using the time step approach. The normalised results are consistent with the values

obtained in laboratory studies and were used in the environmental modelling of surface water and

groundwater fate of penflufen. Accumulated PEC soil was calculated for penflufen and its soil

metabolites M01 and M02. The plateau for penflufen was calculated to be reached after 22 years

assuming application every two years. Additionally, the RMS calculated the accumulated level for the

metabolites M01 and M02. The anaerobic route of degradation in soil was investigated in one soil.


EFSA Journal 2012;10(8):2860 10

Decline of penflufen under anaerobic conditions is significantly slower than under aerobic conditions.

Photolysis in soil was not investigated. The representative use (potato seed treatment) involves

incorporation at planting and the data waiver was initially accepted for this use. Nevertheless a

laboratory soil photolysis would be needed to adequately interpret field studies, in particular residue

trials in which the product was not incorporated. With respect to the environmental assessment, a

particular condition of use has been identified indicating that the data available only cover the

assessment of uses with immediate incorporation and no direct exposure of the product to sunlight.

Batch adsorption/desorption experiments are available in five soils with penflufen and M01 and M02.

The range of pHs of the soils used for experiments with penflufen and M01 is rather narrow covering

only the acidic range (for penflufen: pHCaCl2 5.2-6.3; for M01: 4.9 – 6.4). The range of pH‟s was

considered during the peer review to adequately represent the type of soils more commonly used for

potato cultivation. According to these studies it may be considered that penflufen exhibits medium

mobility in soil, M01 high to very high mobility and M02 low to immobile in acidic soils. Mobility in

alkaline soils is not addressed by the available data.

Penflufen is stable to aqueous hydrolysis at 50 °C in the range pH 4-9. Aqueous photolysis

experiments show some contribution via photolysis to the degradation of penflufen (equivalent to a

DT50 = 84.5 d – 163.6 summer d depending on the latitude). In pH 7 buffered water and after 5.73 d of

continuous irradiation, 77.6 % AR remained as untransformed penflufen and up to 39 different

metabolites were detected with a maximum individual content of 4.8 % AR. In the sterilized natural

water experiments (70 h continuous irradiation equivalent to 27.1 d in Tokyo) two metabolites were

identified: M58 and 5-fluoro-1,3 dimethyl-1H-pyrazole-4-carboxylic acid. The level of these

metabolites was still increasing at the end of the study when a considerable amount of penflufen

remained untransformed. The applicant attributed the occurrence of these metabolites to indirect

photolysis and considered that they would be degraded and transient in a non-sterilized natural system.

However, due to the lack of experimental data to fully confirm these assumptions an assessment of the

potential worst case exposure of surface water has been presented by the applicant based on parent

FOCUS Step 3 PECSW (FOCUS, 2001). In the absence of a readily biodegradation study it is proposed

to consider penflufen not readily biodegradable. Dissipation/degradation of penflufen was investigated

in two water / sediment systems. Rate of partition of penflufen to the sediment phase is variable and

seems to be related to the clay and organic matter content of the sediment. Penflufen degrades slowly

in the whole system (DT50 whole system = 170 – 295 d). Only one metabolite M01 exceeds 10 % AR in the

water phase of some of the experiments. PEC SW / sed have been calculated up to FOCUS Step 3 for

penflufen and up to FOCUS Step 2 for metabolite M01.

Potential groundwater contamination was assessed for penflufen and its soil metabolites M01 and M02

by calculation of the 20 years 80th percentile annual average concentration at 1 m depth using FOCUS

GW models and scenarios (FOCUS-PEARL 3.3.3 and FOCUS-PELMO 3.3.2)8(FOCUS, 2000). For

parent compound simulations, a penflufen geometric mean half-life of 113 d was used considering the

slow phase of the DFOP kinetic analysis for the soil that was not fitted with SFO kinetics. For

metabolites simulation, a penflufen geometric mean half-life of 63 d was used considering the fast

phase of the DFOP kinetic analysis for the soil that was not fitted with SFO kinetics, in order to take

what may be assumed to represent the worst case option with respect to the metabolites calculation.

Use in potatoes was simulated assuming a potato crop will be planted only once every three years in a

given field. According to the RMS, three years rotation instead of two were needed in order to ensure

that the penflufen leachate concentration was below the limit of 0.1 µg/l in a majority of scenarios (see

reporting table 4(47)). Under these conditions, the limit of 0.1 µg/l was exceeded only for 1 of 9

scenarios when PEARL model was used. The limit of 0.1 µg/l was exceeded by metabolite M01 in all

9 scenarios when simulated with PEARL and the accepted default uptake factor of 0. A critical area of

concern was identified for potential groundwater contamination by metabolite M01. In this case the

level of 0.75 µg/l was exceeded in 7 of the 9 scenarios. Metabolite M02 did not exceed the limit of 0.1

8 Simulations complied with EFSA (EFSA, 2004) and correctly utilised the agreed Q10 of 2.58 (following

EFSA, 2007) and Walker equation coefficient of 0.7.


EFSA Journal 2012;10(8):2860 11

µg/l for any of the scenarios simulated. Due to the narrow pH for which soil adsorption/desorption

experiments are available, it cannot be considered that the current assessment will cover the situations

in which the soil is more neutral or alkaline.

5. Ecotoxicology

The risk assessment considered the following documents: European Commission, 2002a, 2002b,

2002c and SETAC, 2001.

It is noted that the environmental fate and behaviour of the isomers of penflufen and its metabolite

M01 has not been separately investigated. Considering however that a sufficient margin of safety has

been identified in the environmental risk assessment for the representative uses evaluated, no further

data were considered to be necessary in relation to the potential enantioselective degradation of

penflufen or its metabolite in the environment.

Considering the representative uses of penflufen, the dietary exposure of herbivorous and

insectivorous birds and mammals via consumption of weeds or ground-dwelling arthropods was

considered to be more likely than the consumption of the unpalatable potato foliage. Therefore, these

scenarios were considered in the risk assessments for herbivorous and insectivorous birds and

mammals considering the potential residue levels of penflufen in feed items (weeds and ground-

dwelling arthropods). It was noted that there is some uncertainty with the available risk assessment as

the residues for weeds and ground-dwelling arthropods have been estimated from residue trials

conducted in late growth stages of potato. It is likely that earlier growth stages would contain higher

residues, but it must be born in mind that residues in weeds and in ground-dwelling arthropods are

coming from indirect uptake from the soil and potato plants and are therefore likely to be low.

Therefore the use of these residue estimates was considered to be reasonable. The risk from direct

consumption of treated potato tubers was also considered using an omnivorous bird, common crane

(Grus grus) and an omnivorous mammal, wild boar (Sus scrofa). On the basis of the available

assessments, a low acute and short-term risk to birds and a low acute and long-term risk to mammals

(considering also the potential for bioaccumulation) was concluded.

The studies that were available for the long-term risk assessments for birds were discussed at the

Pesticides Peer Review experts‟ meeting PPR 91. As agreed in the meeting, the RMS has re-evaluated

the results from the reproduction study on mallard duck (United Kingdom, 2012), but no chronic

endpoint could be established since treatment-related effects could not be excluded at the lowest

treatment level. Therefore, the long-term risk assessment for birds could not be performed with the

available data and a data gap was identified.

A low risk to aquatic organisms was concluded for both the parent penflufen and its metabolites M01

and M02. No toxicity data were available for the photolytic metabolites M58 and 5-fluoro-1,3

dimethyl-1H-pyrazole-4-carboxylic acid. Based on the assumption of a 10 fold higher toxicity of these

metabolites than the parent penflufen, a low risk to aquatic organisms was concluded.

Since penflufen is used as a seed treatment in potato, the HQ approach for the risk characterisation for

bees was not considered to be appropriate. However considering the representative uses and the

toxicological profile of penflufen (acute oral and contact LD50 >100 µg a.s./bee) low risk via contact

exposure was concluded for bees. Regarding the oral route of exposure, the RMS conducted a risk

assessment for foraging bees using an EPPO guidance (EPPO, 2010) and concluded that the risk via

this route of exposure may also be considered as low. Additionally, it is noted that potato flowers are

not considered to be attractive to honeybees.

For the risk assessment for non-target arthropods, standard laboratory studies on the standard species

were available. The risk to non-target arthropods was assessed as low on the basis of low toxicity at an

application rate which exceeded the intended application rates. This conclusion was supported by the

available risk assessments for soil-dwelling organisms that included assessments for soil mites and

collembola.


EFSA Journal 2012;10(8):2860 12

To support the risk assessment for soil macroorganisms, a set of standard laboratory studies on

earthworms, soil mites and collembola were available for penflufen and its soil metabolites. The risk

assessments based on the endpoints derived from these studies indicated a low risk to non-target soil

macroorganisms. Also, a low risk to soil microorganisms could be concluded considering the available

studies.

Due to low exposure for the representative use as a seed treatment in potato, a low risk to non-target

terrestrial plants and to the biological methods for sewage treatment could be concluded. Additionally,

a low toxicity of penflufen to microorganisms in sewage sludge was indicated by a laboratory study.


EFSA Journal 2012;10(8):2860 13

6. Overview of the risk assessment of compounds listed in residue definitions triggering assessment of effects data for the environmental

compartments

6.1. Soil

Compound

(name and/or code) Persistence Ecotoxicology

penflufen

High to very high

(DT50 20 °C pF2= 115 - 336 d)

Risk to soil organisms was assessed as low

M01

Moderate to very high

(DT50 20 °C pF2= 40 – 314 d)


M02

High

(DT50 20 °C pF2= 115 – 254 d)


6.2. Ground water

Compound

(name and/or code) Mobility in soil

>0.1 μg/L 1m depth for

the representative uses (at least one FOCUS

scenario or relevant

lysimeter)

Pesticidal activity Toxicological relevance Ecotoxicological

activity

penflufen

medium mobility

(KFoc = 209.6 – 409.5 mL / g)

FOCUS GW: Yes, 1

scenario with PEARL

model assuming

application once every

third year.

Yes Yes

Risk to aquatic

organisms was assessed

as low


EFSA Journal 2012;10(8):2860 14

M01

high to very high mobility

(KFoc = 26.1 – 61.9 mL/g)

FOCUS GW: Yes, 9/9

scenarios exceed 0.1 μg/L

with 7/9 scenarios

exceeding 0.75 μg/L with

PEARL in the RMS

calculation (plant uptake

factor = 0) assuming

application once every

third year.

No sufficient data

available

Yes,

based on the classification

of penflufen as

Carcinogenic, Carc cat 2

(GHS) discussed during

the meeting. To be

confirmed by EChA

Risk to aquatic


as low

M02

low to immobile

(KFoc = 863.2 – 6033.4 mL/g)

FOCUS GW: No,

assuming application once

every third year.

No sufficient data

available No assessment needed

Risk to aquatic


as low

6.3. Surface water and sediment

Compound

(name and/or code) Ecotoxicology

penflufen Risk to aquatic organisms was assessed as low

M01 Risk to aquatic organisms was assessed as low



5-fluoro-1,3 dimethyl-1H-pyrazole-4-carboxylic acid Risk to aquatic organisms was assessed as low

6.4. Air

Compound

(name and/or code) Toxicology


EFSA Journal 2012;10(8):2860 15

penflufen Not acutely toxic after inhalation


EFSA Journal 2012;10(8):2860 16

7. List of studies to be generated, still ongoing or available but not peer reviewed

This is a complete list of the data gaps identified during the peer review process, including those areas

where a study may have been made available during the peer review process but not considered for

procedural reasons (without prejudice to the provisions of Article 7 of Directive 91/414/EEC

concerning information on potentially harmful effects).

Method of analysis for M01 in groundwater (relevant for all representative uses evaluated; no

submission date proposed; see section 1).

The toxicological relevance of the impurities in the proposed specification needs to be addressed

(relevant for all representative uses evaluated; data gap identified during the expert meeting; no

submission date proposed; see section 2).

Rotational crop field trials on cereals, leafy vegetables, root vegetables and soybean at a dose rate

covering the calculated plateau concentration of penflufen in soil in order to determine the residue

levels of penflufen and metabolites M01 (free and conjugated), M49, M58, M63, M64 and M65.

(relevant for all representative uses evaluated; no submission date proposed; see section 3).

Photolysis in soil study is needed to adequately interpret field studies, in particular field residue

trials in which the product was not incorporated (no submission date proposed; see section 4).

The long-term risk to birds needs to be further addressed (relevant for all representative uses

evaluated; no submission date proposed; see section 5).

8. Particular conditions proposed to be taken into account to manage the risk(s) identified

Coveralls and protective gloves when handling the concentrate, contaminated surfaces and freshly

treated material have to be worn by operators to reach exposure levels below the AOEL for the

roller table method; considering the uncertainty of the enantiomer issue for re-entry workers (see

section 2) the use of gloves is recommended to further decrease the exposure level.

Current assessment only addresses use as a seed treatment (prior to planting) on potatoes planted

every third year.

In the absence of a soil photolysis study, only uses where the product is immediately incorporated

in soil and not exposed to light are covered by the available data and assessment.

9. Concerns

9.1. Issues that could not be finalised

An issue is listed as an issue that could not be finalised where there is not enough information

available to perform an assessment, even at the lowest tier level, for the representative uses in line

with the Uniform Principles of Annex VI to Directive 91/414/EEC and where the issue is of such

importance that it could, when finalised, become a concern (which would also be listed as a critical

area of concern if it is of relevance to all representative uses).

1. The consumer dietary risk assessment could not be finalised since no conclusion could be drawn

on the residue definitions in rotational crops and whether MRLs are needed on these crops.

2. The long-term risk assessment for birds could not be performed with the available information.


EFSA Journal 2012;10(8):2860 17

9.2. Critical areas of concern

An issue is listed as a critical area of concern where there is enough information available to perform

an assessment for the representative uses in line with the Uniform Principles of Annex VI to Directive

91/414/EEC, and where this assessment does not permit to conclude that for at least one of the

representative uses it may be expected that a plant protection product containing the active substance

will not have any harmful effect on human or animal health or on groundwater or any unacceptable

influence on the environment.

An issue is also listed as a critical area of concern where the assessment at a higher tier level could not

be finalised due to a lack of information, and where the assessment performed at the lower tier level

does not permit to conclude that for at least one of the representative uses it may be expected that a

plant protection product containing the active substance will not have any harmful effect on human or

animal health or on groundwater or any unacceptable influence on the environment.

3. Groundwater contamination by relevant metabolite M01 (based on the carcinogenic potential of

penflufen, to be decided by EChA in accordance with the requirements of Regulation 1278/2008)

indicated at all 9 FOCUS scenarios.


EFSA Journal 2012;10(8):2860 18

9.3. Overview of the concerns identified for each representative use considered

(If a particular condition proposed to be taken into account to manage an identified risk, as listed in

section 8, has been evaluated as being effective, then „risk identified‟ is not indicated in this table.)

Representative use Tuber treatment before planting or on-planter spray at planting

Operator risk

Risk identified

Assessment not

finalised

Worker risk

Risk identified

Assessment not

finalised

Bystander risk

Risk identified

Assessment not

finalised

Consumer risk

Risk identified

Assessment not

finalised X

1

Risk to wild non

target terrestrial

vertebrates

Risk identified

Assessment not

finalised X

2

Risk to wild non

target terrestrial

organisms other

than vertebrates

Risk identified

Assessment not

finalised

Risk to aquatic

organisms

Risk identified

Assessment not

finalised

Groundwater

exposure active

substance

Legal

parametric value

breached 1/9 scenarios

Assessment not

finalised

Groundwater

exposure

metabolites

Legal

parametric value

breached X

3

Parametric

value of

10µg/L(a)

breached

Assessment not

finalised

Comments/Remarks

The superscript numbers in this table relate to the numbered points indicated in sections 9.1 and 9.2. Where there is no

superscript number see sections 2 to 6 for further information.

(a): Value for non-relevant metabolites prescribed in SANCO/221/2000-rev 10-final, European Commission, 2003


EFSA Journal 2012;10(8):2860 19

REFERENCES

EFSA (European Food Safety Authority), 2004. Opinion of the Scientific Panel on Plant Health, Plant

Protection Products and their Residues on a request of EFSA related to FOCUS groundwater

models comparability and the consistency of this risk assessment of groundwater contamination.

The EFSA Journal (2004) 93, 1-20.

EFSA (European Food Safety Authority), 2007. Scientific Opinion of the Panel on Plant Protection

Products and their Residues on a request from EFSA related to the default Q10 value used to

describe the temperature effect on transformation rates of pesticides in soil. The EFSA Journal

(2007) 622, 1-32.

EFSA (European Food Safety Authority), 2012. Peer Review Report to the conclusion regarding the

peer review of the pesticide risk assessment of the active substance penflufen.

EPPO, 2010. A. Alix et. al. Guidance for the assessment of risks to bees from the use of plant

protection products under the framework of Council Directive 91⁄414 and Regulation 1107⁄2009,

2010 OEPP/EPPO, Bulletin OEPP/EPPO Bulletin 40, 196–203.

European Commission, 1999. Guidelines for the generation of data concerning residues as provided in

Annex II part A, section 6 and Annex III, part A, section 8 of Directive 91/414/EEC concerning

the placing of plant protection products on the market, 1607/VI/97 rev.2, 10 June 1999.

European Commission, 2000. Technical Material and Preparations: Guidance for generating and

reporting methods of analysis in support of pre- and post-registration data requirements for Annex

II (part A, Section 4) and Annex III (part A, Section 5) of Directive 91/414. SANCO/3030/99

rev.4, 11 July 2000.

European Commission, 2002a. Guidance Document on Terrestrial Ecotoxicology Under Council

Directive 91/414/EEC. SANCO/10329/2002 rev.2 final, 17 October 2002.

European Commission, 2002b. Guidance Document on Aquatic Ecotoxicology Under Council

Directive 91/414/EEC. SANCO/3268/2001 rev 4 (final), 17 October 2002.

European Commission, 2002c. Guidance Document on Risk Assessment for Birds and Mammals

Under Council Directive 91/414/EEC. SANCO/4145/2000.

European Commission, 2001. Guidelines on comparability, extrapolation, group tolerances and data

requirements for setting MRLs. SANCO Doc 7525/VI/95-rev.9. pp.1-46.

European Commission, 2003. Guidance Document on Assessment of the Relevance of Metabolites in

Groundwater of Substances Regulated under Council Directive 91/414/EEC. SANCO/221/2000-

rev. 10 - final, 25 February 2003.

European Commission, 2004. Guidance document on residue analytical methods. SANCO/825/00

rev. 8.1, 17 March 2004.

European Commission, 2009. Guidance Document on the Assessment of the Equivalence of

Technical Materials of Substances Regulated under Council Directive 91/414/EEC.

SANCO/10597/2003 – rev. 8.1, May 2009.

FOCUS, 2000. “FOCUS Groundwater Scenarios in the EU review of active substances”. Report of

the FOCUS Groundwater Scenarios Workgroup, EC Document Reference SANCO/321/2000-

rev.2. 202 pp, as updated by the Generic Guidance for FOCUS groundwater scenarios, version 1.1

dated April 2002.

FOCUS, 2001. “FOCUS Surface Water Scenarios in the EU Evaluation Process under 91/414/EEC”.

Report of the FOCUS Working Group on Surface Water Scenarios, EC Document Reference

SANCO/4802/2001-rev.2. 245 pp., as updated by the Generic Guidance for FOCUS surface water

scenarios, version 1.1 dated March 2012


EFSA Journal 2012;10(8):2860 20

FOCUS, 2006. “Guidance Document on Estimating Persistence and Degradation Kinetics from

Environmental Fate Studies on Pesticides in EU Registration” Report of the FOCUS Work Group

on Degradation Kinetics, EC Document Reference Sanco/10058/2005 version 2.0, 434 pp.

JMPR, 2004. Report of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food

and the Environment and the WHO Core Assessment Group on Pesticide Residues Rome, Italy,

20–29 September 2004, Report 2004, 383 pp.

JMPR, 2007. Report of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food

and the Environment and the WHO Core Assessment Group on Pesticide Residues Geneva,

Switzerland, 18–27 September 2007, Report 2007, 164 pp.

SETAC (Society of Environmental Toxicology and Chemistry), 2001. Guidance Document on

Regulatory Testing and Risk Assessment procedures for Plant Protection Products with Non-

Target Arthropods. ESCORT 2.

United Kingdom, 2011. Draft Assessment Report (DAR) on the active substance penflufen prepared

by the rapporteur Member State the United Kingdom in the framework of Directive 91/414/EEC,

August 2011.

United Kingdom, 2012. Final Addendum to Draft Assessment Report on penflufen, compiled by

EFSA, May 2012.


EFSA Journal 2012;10(8):2860 21

APPENDICES

APPENDIX A – LIST OF END POINTS FOR THE ACTIVE SUBSTANCE AND THE REPRESENTATIVE

FORMULATION

Identity, Physical and Chemical Properties, Details of Uses, Further Information

Active substance (ISO Common Name) ‡ Penflufen

Function (e.g. fungicide) Fungicide

Rapporteur Member State United Kingdom

Co-rapporteur Member State N/A

Identity (Annex IIA, point 1)

Chemical name (IUPAC) ‡ 2'-[(RS)-1,3-dimethylbutyl]-5-fluoro-1,3-

dimethylpyrazole-4-carboxanilide

Chemical name (CA) ‡ N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-

dimethyl-1H-pyrazole-4-carboxamide

CIPAC No ‡ 826

CAS No ‡ 494793-67-8

EC No (EINECS or ELINCS) ‡ Not allocated

FAO Specification (including year of

publication) ‡

Not applicable

Minimum purity of the active substance as

manufactured ‡

950 g/kg (N.B Based on pilot scale production)

1:1 (R:S) ratio of enantiomers

Identity of relevant impurities (of

toxicological, ecotoxicological and/or

environmental concern) in the active

substance as manufactured

Open

Molecular formula ‡ C18H24FN3O

Molecular mass ‡ 317.41 g/mol

Structural formula ‡

NH

CH3

CH3

CH3

N

CH3

CH3

F

O

N


EFSA Journal 2012;10(8):2860 22

Physical and chemical properties (Annex IIA, point 2)

Melting point (state purity) ‡ 111.1 °C ( 99.2% pure)

Boiling point (state purity) ‡ Penflufen (99.2% pure) has no boiling point at

atmospheric pressure and decomposition starts

at ca. 320 °C.

Temperature of decomposition (state

purity)

Penflufen (99.2% pure) shows an endothermic

effect in the temperature range of 100-130 °C

(melting) and an exothermal decomposition in the

temperature range of 320-400 °C with an energy of

174 J/g or 221 J/g, respectively.

Appearance (state purity) ‡ Penflufen (99.2% pure material as

manufactured) is an off white powder with a

weak odour.

Vapour pressure (state temperature, state

purity) ‡

Extrapolated vapour pressures for penflufen

(99.2% pure) are:

4.1 x 10-7

Pa at 20 °C

1.2 x 10-6

Pa at 25 °C

1.7 x 10-4

Pa at 50 °C

Henry‟s law constant ‡ The calculated Henry‟s law constants (K) of

penflufen at 20 °C in the aqueous phase are:

pH 6.5 (dist. wat.): K = 1.05 x 10-5

Pa m3 mol

-1

pH 4.0 (buffered): K = 1.18 x 10-5

Pa m3 mol

-1

pH 7.1 (buffered): K = 1.19 x 10-5

Pa m3 mol

-1

pH 8.9 (buffered): K = 1.16 x 10-5

Pa m3 mol

-1

Solubility in water (state temperature, state

purity and pH) ‡

Water solubility (Cs) of penflufen (99.2% pure)

at 20 °C:

Distilled water at pH 6.5: 12.4 mg/L

Buffer at pH 4: 11.0 mg/L



Solubility in organic solvents ‡

(state temperature, state purity)

Solubility of penflufen (99.2% pure) in organic

solvents at 20 °C:

methanol: 126 g/L

heptane: 1.6 g/L

toluene: 62 g/L

dichloromethane: >250 g/L

acetone: 139 g/L

ethyl acetate: 96 g/L

dimethyl sulfoxide: 162 g/L

The test item is classified as being „readily

soluble‟


EFSA Journal 2012;10(8):2860 23

Surface tension ‡

(state concentration and temperature, state

purity)

61.6 mN/m at 20 °C (98.1% technical)

The test item is not surface active (i.e. surface

tension is not <60 mN/m at 20 °C).

N.B. The solubility of the test item in distilled

water is <1 g/L (12.4 mg/L at 20 °C).

Therefore, saturated solutions were prepared

and subsequently diluted to 90% of the

saturated concentration.

Partition co-efficient ‡

(state temperature, pH and purity)

The n-octanol/water partition coefficients (Pow)

of penflufen (99.2%) at 25 °C were:

pH 4: Pow = 1995, log Pow = 3.3

pH 7: Pow = 1995, log Pow = 3.3

pH 9: Pow = 1995, log Pow = 3.3

Dissociation constant (state purity) ‡ No dissociation constant (pKa) was found in an

aqueous solution of penflufen (99.2% pure) in

the range of 1 < pKa <12.

UV/VIS absorption (max.) incl. ‡

(state purity, pH)

Purity: 98.1% technical

Range of wavelength: 200-800 nm

Solvent: acetonitrile

Peak maxima [nm] Molar absorption

[1000 cm2/mol]

209 23723.86

232 (shoulder) 10938.90

Solvent: acetonitrile/buffer solution (pH 2)


[1000 cm2/mol]

202 25029.68

230 (shoulder) 11784.16

Solvent: acetonitrile/buffer solution (pH 10)


[1000 cm2/mol]

204 23009.69

234 (shoulder) 9867.96

In all solvent systems there is no significant

absorption/peak maxima at >290 nm.


EFSA Journal 2012;10(8):2860 24

Flammability ‡ (state purity) Not a highly flammable solid (98.1%

technical).

No self-ignition was observed up to melting

and up to the maximum temperature of 403 °C.

Therefore penflufen is not a self-igniting solid.

Explosive properties ‡ (state purity) Not explosive (98.1% technical).

Oxidising properties ‡ (state purity) Not oxidising (98.1% technical).


EFSA Journal 2012;10(8):2860 25

Summary of representative uses evaluated (Penflufen)

Crop and/

or situation

Member

State

or

Country

Product

name

F

G

or

I

Pests or

Group of pests

controlled

Preparation

Application

Application rate per treatment

(for explanation see the text in front of this section)

PHI

(days)

Remarks

(a)

(b)

(c)

Type

(d-f)

Conc.

of as

(i)

method

kind

(f-h)

growth

stage &

season

(j)

numb

er

min/ max

(k)

interval

between

applications (min)

g as/hL

min – max (l)

water

L/ha

min –

max

g as/ha

min – max (l)

(m)

Potato (ware)

EU North South

BYF 14182 FS 050

FI Thanatephorus cucumeris

FS 50 g/l

Seed treatment –

indoor roller table application before

planting or outdoor

on-planter spray at planting

from 00 to 03

1 not applicable

0.4 L product / tonne potato seed

Product applied neat or diluted in 1.5 – 3 l water / tonne seed

Rate equivalent to 20 g as/tonne seed

Planting rate equivalent to 2 – 3 tonnes

potatoes/ha therefore 40 – 60 g as/ha

_ 2-3 tonnes of tuber/ha for ware potatoes every 3 years

Potato (seed and

salad)

EU North South

BYF 14182 FS 050

FI Thanatephorus cucumeris

FS 50 g/l

Seed treatment –

indoor roller table application before

planting or outdoor

on-planter spray at

planting

from 00 to 03

1 not applicable

0.4 L product / tonne potato seed

Product applied neat or diluted in 1.5 – 3 l water / tonne seed

Rate equivalent to 20 g as/tonne seed

Planting rate equivalent to 5 tonnes

potatoes/ha therefore 100 g as/ha

_ 5 tonnes of tuber/ha for daughter tuber production (seed) and salad potatoes every 3 years

Uses should be crossed out when the notifier no longer supports this use(s). (a) For crops, the EU and Codex classifications (both) should be taken into account; where relevant, the use

situation should be described (e.g. fumigation of a structure)

(b) Outdoor or field use (F), greenhouse application (G) or indoor application (I) (c) e.g. biting and suckling insects, soil born insects, foliar fungi, weeds

(d) e.g. wettable powder (WP), emulsifiable concentrate (EC), granule (GR)

(e) GCPF Codes - GIFAP Technical Monograph No 2, 1989 (f) All abbreviations used must be explained

(g) Method, e.g. high volume spraying, low volume spraying, spreading, dusting, drench

(h) Kind, e.g. overall, broadcast, aerial spraying, row, individual plant, between the plant- type of equipment

used must be indicated

(i) g/kg or g/L. Normally the rate should be given for the active substance (according to ISO) and not for the variant in order to compare the rate for same active substances used in different variants (e.g.

fluoroxypyr). In certain cases, where only one variant is synthesised, it is more appropriate to give

the rate for the variant (e.g. benthiavalicarb-isopropyl). (j) Growth stage at last treatment (BBCH Monograph, Growth Stages of Plants, 1997, Blackwell, ISBN 3-

8263-3152-4), including where relevant, information on season at time of application

(k) Indicate the minimum and maximum number of application possible under practical conditions of use (l) The values should be given in g or kg whatever gives the more manageable number (e.g. 200 kg/ha

instead of 200 000 g/ha or 12.5 g/ha instead of 0.0125 kg/ha

(m) PHI - minimum pre-harvest interval


EFSA Journal 2012;10(8):2860 26

Methods of Analysis

Analytical methods for the active substance (Annex IIA, point 4.1)

Technical as (analytical technique) GC/MS

Impurities in technical as (analytical

technique)

GC/MS

Plant protection product (analytical

technique)

HPLC/UV (detection at 240 nm)

Analytical methods for residues (Annex IIA, point 4.2)

Residue definitions for monitoring purposes

Food of plant origin Penflufen (sum of isomers) Open for rotational

crops

Food of animal origin Open

Soil Penflufen (sum of isomers)

Water surface Penflufen (sum of isomers)

drinking/ground Penflufen (sum of isomers), M01

Air Penflufen (sum of isomers)

Monitoring/Enforcement methods

Food/feed of plant origin (analytical

technique and LOQ for methods for

monitoring purposes)

LC-MS/MS (LOQ = 0.01 mg/kg)

Matrix: lettuce, potato, dry bean, carrot, barley

and orange.

An ILV was performed on potato, dry bean,

barley and orange.

N.B. Sunflower seeds were also analysed for

penflufen residues although low recoveries

were generally observed. Therefore the method

is not suitable for the detection of penflufen in

oily matrices.

The analytical method provides information on

two separate MS transitions (i.e. for

quantification and confirmation), and as such,

is deemed to be a highly specific method.


EFSA Journal 2012;10(8):2860 27

Food/feed of animal origin (analytical

technique and LOQ for methods for

monitoring purposes)

Not applicable

Soil (analytical technique and LOQ)

LC-MS/MS (LOQ = 5 µg/kg)

Water (analytical technique and LOQ)

LC-MS/MS (LOQ = 0.05 µg/L)

Matrix: surface water*

Open for a method of analysis for the

metabolite M01 in ground water

* For method validation surface water from the

river Rhine sampled in Leverkusen-Hitdorf was

used.

Air (analytical technique and LOQ)

LC-MS/MS (LOQ = 4.0 µg/m3)

Body fluids and tissues (analytical

technique and LOQ)

Not applicable as the active substance is not

classified as toxic or very toxic.

Classification and proposed labelling with regard to physical and chemical data (Annex IIA,

point 10)

RMS/peer review proposal

Active substance None


EFSA Journal 2012;10(8):2860 28

Impact on Human and Animal Health

Absorption, distribution, excretion and metabolism (toxicokinetics) (Annex IIA, point 5.1)

Rate and extent of oral absorption ‡ Rapid (tmax ≤ 1.5 hours) and extensive (90-

100%)

Distribution ‡ Widespread, with the highest concentrations

being present in the liver, erythrocytes, kidney

and adrenals of both sexes and the brown fat of

females.

Potential for accumulation ‡ Low

Rate and extent of excretion ‡ Rapid and extensive, with excretion being

almost complete after 2-3 days

Metabolism in animals ‡ Extensive. Mainly to pyrozole ring

demethylated products or by hydroxylation to

trihydroxy and dihydroxy compounds.

Toxicologically relevant compounds ‡

(animals and plants)

Parent compound and metabolites

Toxicologically relevant compounds ‡

(environment)

Parent compound and metabolites

Acute toxicity (Annex IIA, point 5.2)

Rat LD50 oral ‡ >2000 mg/kg

Rat LD50 dermal ‡ >2000 mg/kg

Rat LC50 inhalation ‡ >2.02 mg/L (4h, nose only, to dust)

Skin irritation ‡ Not irritating

Eye irritation ‡ Not irritating

Skin sensitisation ‡ Not sensitising (M&K test)

Short term toxicity (Annex IIA, point 5.3)

Target / critical effect ‡ Principal targets are the liver (diffuse

centrilobular hepatocellular hypertrophy and

increased organ weight) and thyroid (diffuse

follicular cell hypertrophy, sometimes

accompanied by focal/multifocal colloid)

Relevant oral NOAEL ‡ 7.7 mg/kg bw per day (1 year study in

dogs)

Relevant dermal NOAEL ‡ 300 mg/kg bw per day (28 day study in

rats)

Relevant inhalation NOAEL ‡ Test not conducted


EFSA Journal 2012;10(8):2860 29

Genotoxicity ‡ (Annex IIA, point 5.4)

Not genotoxic (negative in an Ames

test, an in vitro mammalian cell gene

mutation test, an in vitro clastogenicity

test and an in vivo micronucleus test)

Long term toxicity and carcinogenicity (Annex IIA, point 5.5)

Target/critical effect ‡ Principal targets are the liver (diffuse

centrilobular hepatocellular hypertrophy and

increased organ weight) and thyroid (diffuse

follicular cell hypertrophy, sometimes

accompanied by focal/multifocal colloid)

Relevant NOAEL ‡ 4 mg/kg bw per day (2 year study in rats)

Carcinogenicity ‡ Carcinogenic, Carc cat 2 (GHS)

proposed by Pesticides Peer Review

Meeting on basis of the presence of

liver adenomas in female rats, ovary

tubulostromal adenomas in rats,

histiocytic sarcoma in male rats, brain

astrocytomas in male rats, liver

carcinomas in male and female mice.

Carcinogenicity NOAEL: 79 and 113

mg/kg bw per day in males & female

rats, respectively

Reproductive toxicity (Annex IIA, point 5.6)

Reproduction toxicity

Reproduction target / critical effect ‡ Reduced bodyweight gain during

lactation, decreased spleen weight,

delayed vaginal opening in F1 and F2

generation pups, in presence of parental

toxicity (2-generation study in rats)

Relevant parental NOAEL ‡ 58 mg/kg bw per day in males and 71

mg/kg bw per day in females (2-

generation study in rats)

Relevant reproductive NOAEL ‡ 58 mg/kg bw per day in males and 71

mg/kg bw per day in females (2-

generation study in rats)

Relevant offspring NOAEL ‡ Parental dose of 58 mg/kg bw per day in

males and 71 mg/kg bw per dayin

females (2-generation study in rats)


EFSA Journal 2012;10(8):2860 30

Developmental toxicity

Developmental target / critical effect ‡ None

Relevant maternal NOAEL ‡ 100 mg/kg bw per day (rat

developmental toxicity study)

Relevant developmental NOAEL ‡ 300 mg/kg bw per day, the highest dose

level tested (rat developmental toxicity

study)

Neurotoxicity (Annex IIA, point 5.7)

Acute neurotoxicity ‡ Minor transient changes observed, as

clinical signs, reduced activity, reduced

body temperature. NOAEL 100 mg/kg

in males and 50 mg/kg bw per day in

females (acute neurotoxicity in rats)

Repeated neurotoxicity ‡ No evidence of neurotoxicity (13 week

neurotoxicity study in rats)

Delayed neurotoxicity ‡ Testing not necessary

Other toxicological studies (Annex IIA, point 5.8)

Mechanism studies ‡ In vitro hepatocyte mode of action studies

show that penflufen is a phenobarbital-like

liver enzyme inducer.

Studies performed on metabolites or

impurities ‡

M01

Negative in an Ames test, an in vitro

mammalian cell gene mutation test and an in

vitro clastogenicity test

M02

Negative in an Ames test, an in vitro

mammalian cell gene mutation test and an in

vitro clastogenicity test

Medical data ‡ (Annex IIA, point 5.9)

No adverse effects suspected or being related to

penflufen have been observed


EFSA Journal 2012;10(8):2860 31

Summary (Annex IIA, point 5.10) Value Study Safety

factor

ADI ‡ 0.04 mg/kg bw

per day

2 year dietary

in rats

100

AOEL ‡ 0.077 mg/kg bw

per day

1 year dietary

in dogs

100

ARfD ‡ 0.5 mg/kg bw Acute oral

neurotoxicity

study in rats

100

Dermal absorption ‡ (Annex IIIA, point 7.3)

Formulation (Penflufen FS 050) 0.21%, 0.21%, 1.45% and 1.20% for penflufen

concentrations of 240, 50, 10 and 1g/L,

respectively.

Exposure scenarios (Annex IIIA, point 7.2)

Operator Higher tier data were used for the operator

assessment.

17% of the AOEL for the in furrow method

with no PPE

10% of the AOEL for the roller table method

with the use of coveralls and protective gloves

when handling the concentrate, contaminated

surfaces and freshly treated materials.

Workers Workers exposed to treated seed potatoes

during planting operations: 48% of the AOEL

The impact of each individual enantiomer on

the toxicity, relevant for the re-entry activities,

was not assessed: however, considering the

worst case that only one enantiomer is

responsible for the recorded toxicity, this

would lead to an exposure of 96% of the

AOEL, which could be further reduced with the

use of gloves.


EFSA Journal 2012;10(8):2860 32

Bystanders Bystander exposure to vapour

Negligible.

Bystander exposure to drift

Application by roller table

Bystanders incidental to the treatment area are

not likely to exist but in any case would be

present for a short duration compared to

cutter/sorters present for a full day and hence

no further estimate of bystander exposure is

necessary.

In-furrow treatment

Unlikely

Classification and proposed labelling with regard to toxicological data (Annex IIA, point 10)

Peer Review Meeting proposal

Substance classified (name) Penflufen: GHS Carc Cat 2


EFSA Journal 2012;10(8):2860 33

Metabolism in plants (Annex IIA, point 6.1 and 6.7, Annex IIIA, point 8.1 and 8.6)

Plant groups covered Root and tuber vegetables (potatoes) (seed and

in-furrow soil treatment)

Rotational crops Cereals (wheat), Pulses/oilseeds (soybean),

Root and tuber vegetables (turnip)

Metabolism in rotational crops similar to

metabolism in primary crops?

No

Preferential cleavage of penflufen either on the

carboxamide linkage or on the N-phenyl bond

in rotational crops at all plant back intervals

after a bare soil application.

Processed commodities Studies not triggered.

Residue pattern in processed commodities

similar to residue pattern in raw

commodities?

Yes

Plant residue definition for monitoring Penflufen (sum of isomers) for root and tuber

vegetables only- Limited to seed and in-furrow

soil treatments.

Open for the rotational crops.

Plant residue definition for risk assessment Penflufen (sum of isomers) for root and tuber

vegetables only- Limited to seed and in-furrow

soil treatments.

Open for the rotational crops.

Conversion factor (monitoring to risk

assessment)

N/A

Metabolism in livestock (Annex IIA, point 6.2 and 6.7, Annex IIIA, point 8.1 and 8.6)

Animals covered Lactating goat, laying hen

Time needed to reach a plateau

concentration in milk and eggs

Goat: 32 hours

Hen: 8 days

Animal residue definition for monitoring Open

Animal residue definition for risk

assessment

Open

Conversion factor (monitoring to risk

assessment)

Open

Metabolism in rat and ruminant similar

(yes/no)

Open

Fat soluble residue: (yes/no) Yes - log Pow = 3.3.


EFSA Journal 2012;10(8):2860 34

Residues in succeeding crops (Annex IIA, point 6.6, Annex IIIA, point 8.5)

Data gap to provide field trials on cereals, leafy

vegetables, root vegetables and soybean at a

dose rate covering the calculated plateau

concentration of penflufen in soil to determine

the residue levels of penflufen, M01 (free and

conjugated), M49, M58, M63, M64 and M65.

Stability of residues (Annex IIA, point 6 introduction, Annex IIIA, point 8 Introduction)

Penflufen and metabolites M01, M49, M58 and

M64 stable (-18°C) for up to 26 months in high

water-, high oil-, high acid- content matrices

and dry commodities.

Residues from livestock feeding studies (Annex IIA, point 6.4, Annex IIIA, point 8.3)

Ruminant: Poultry: Pig:

Conditions of requirement of feeding studies

Expected intakes by livestock 0.1 mg/kg

diet (dry weight basis) (yes/no - If yes,

specify the level)

Open Open Open

Potential for accumulation (yes/no): Considered to

be low, fast

plateau and

high level of

excretion.

Considered to

be low, fast

plateau and

high level of

excretion.

Metabolism studies indicate potential level

of residues ≥ 0.01 mg/kg in edible tissues

(yes/no)

Open Open Open

Feeding studies (Specify the feeding rate in

cattle and poultry studies considered as

relevant)

Residue levels in matrices : Mean (max)

mg/kg

Muscle Feeding studies not submitted.

Liver

Kidney

Fat

Milk

Eggs


EFSA Journal 2012;10(8):2860 35

Summary of residues data according to the representative uses on raw agricultural commodities and feedingstuffs (Annex IIA, point 6.3, Annex

IIIA, point 8.2)

Crop Northern or

Mediterranean

Region, field or

glasshouse, and

any other useful

information

Trials results relevant to the

representative uses

(a)

Recommendation/comments MRL estimated

from trials

according to the

representative

use

(mg/kg)

HR

(mg/kg)

(c)

STMR

(mg/kg)

(b)

Potato

(Seed treatment)

N EU Tuber: 9 x <0.01 mg/kg

0.01*

0.01 0.01

Potato

(Seed treatment)

S EU Tuber: 9 x <0.01 mg/kg 0.01*

0.01 0.01

(a) Numbers of trials in which particular residue levels were reported e.g. 3 x <0.01, 1 x 0.01, 6 x 0.02, 1 x 0.04, 1 x 0.08, 2 x 0.1, 2 x 0.15, 1 x

0.17

(b) Supervised Trials Median Residue i.e. the median residue level estimated on the basis of supervised trials relating to the representative use

(c) Highest residue


EFSA Journal 2012;10(8):2860 36

Consumer risk assessment (Annex IIA, point 6.9, Annex IIIA, point 8.8)(1)

ADI 0.04 mg/kg bw per day

TMDI (% ADI) according to EFSA

PRIMo Model

<1% of ADI

TMDI (% ADI) according to national (to

be specified) diets

<1% of ADI (calculated using UK chronic

version 1.1)

Factors included in IEDI and NEDI None

ARfD 0.5 mg/kg bw

IESTI (% ARfD) according to EFSA

PRIMo Model

<1% of ARfD

NESTI (% ARfD) according to national (to

be specified) large portion consumption

data

<1% of ARfD (calculated using UK acute

version 1.2)

Factors included in IESTI and NESTI None

(1)The consumer risk assessment has to be regarded as provisional pending the final residue

definition and the potential need for MRLs in rotational crops.

Processing factors (Annex IIA, point 6.5, Annex IIIA, point 8.4)

Crop/ process/ processed product

Number of

studies

Processing factors Amount

transferred

(%)

(Optional)

Transfe

r factor

Yield

factor

Potato

Not required as

residues <0.01

mg/kg


EFSA Journal 2012;10(8):2860 37

Proposed MRLs (Annex IIA, point 6.7, Annex IIIA, point 8.6)

Potatoes

0.01* mg/kg

When the MRL is proposed at the LOQ, this should be annotated by an asterisk after the figure.


EFSA Journal 2012;10(8):2860 38

Route of degradation (aerobic) in soil (Annex IIA, point 7.1.1.1.1)

Mineralization after 100 days ‡

Phenyl-label (A): 1.5 – 6.5% AR after 120 days

Pyrazole-label (B): 1.4 – 2.7% AR after 120

days

(Linear interpolation for 100 days:

Phenyl-label (A): 1.3 – 5.2% AR

Pyrazole-label (B): 1.5 – 1.9% AR

Values from interpolation between sampling

point just prior to 100 days and the last

sampling,

i.e. between 58 and 120 days for label A, and

between 90 and 120 days for label B)

Non-extractable residues after 100 days ‡

Phenyl-label (A): 8.8 – 19.3% AR after 120

days

Pyrazole-label (B): 10.1 – 13.2% AR after 120

days

(Linear interpolation for 100 days:

Phenyl-label (A): 8.4 – 13.6% AR

Pyrazole-label (B): 8.0 – 12.9% AR

Values from interpolation between sampling

point just prior to 100 days and the last

sampling,

i.e. between 58 and 120 days for label A, and

between 90 and 120 days for label B)

Metabolites requiring further consideration

‡ - name and/or code, % of applied (range

and maximum)

penflufen-3-hydroxy-butyl (max. 17.0 % AR)

penflufen-pyrazolyl-AAP (max. 11.5% AR)

Route of degradation in soil - Supplemental studies (Annex IIA, point 7.1.1.1.2)

Anaerobic degradation Following an aerobic ageing period penflufen

showed only moderate degradation under

anaerobic conditions of the test. No major

transformation products were detected for

either label. Slow conversion was accompanied

by formation of non-extractable residues and

small amounts of volatile components.

Formation of CO2 including other volatiles was

1.0% / 0.4% (phenyl-/ pyrazole-label) during

the study.

Soil photolysis No tests were performed regarding the

phototransformation of penflufen due to its

intended use in seed treatment of potatoes only.

The active substance is thus not directly

exposed to sunlight.


EFSA Journal 2012;10(8):2860 39

Rate of degradation in soil (Annex IIA, point 7.1.1.2, Annex IIIA, point 9.1.1)

Laboratory studies ‡

Penflufen Aerobic conditions („modelling‟* endpoints only shown for clarity -

trigger endpoints always exceeded the 60 d trigger)

Soil type pH

(CaCl2

)

t. oC / %

MWHC

DT50 /DT90

(under study

conditions)

DT50

(20°C,

pF2)a

χ2 Method of

calculation

Hoefchen am Hohenseh

– silt loam – phenyl

label

6.7 20°C/54% of

MWHC

115/382 115 1.8 SFO

Laacherhof, AXXa –

sandy loam – phenyl

label

6.4 20°C/54% of

MWHC

162/538 162 1.6 SFO

Laacherhof,

Wurmwiese –loam –

phenyl label

5.4 20°C/54% of

MWHC

239/793 239 2.4 SFO

Laacherhof, AIIIa –

loam – phenyl label

6.6 20°C/54% of

MWHC

128/425 128 1.9 SFO

Springfield, Nebraska -

silt loam -phenyl label

6.5 25°C/75% of

1/3 bar

235/780 260 5.5 SFO

Springfield, Nebraska -

silt loam - pyrazole

label

6.5 25°C/75% of

1/3 bar

270/896 299 3.2 SFO

Porterville, California –

sandy loam - phenyl

label

7.7 25°C/75% of

1/3 bar

409/1358 300 1.6 SFO

Porterville, California –

sandy loam - pyrazole

label

7.7 25°C/75% of

1/3 bar

458/1521 336 1.7 SFO

Geometric mean 226/750 192b - -

*note these values were not actually used for modelling since information from field dissipation studies were

used in the parent exposure assessment. aNo correction was required for the EU soils since studies were performed at 20°C and greater than pF2 based

on the default moisture contents from the FOCUS groundwater report. bOverall geometric mean calculated after derivation of individual geomeans for the separate label positions for

the Springfield and Porterville soils.

M01 metabolite Aerobic conditions (modelling

endpoints only for M01)

Soil type pH

(CaCl2)

t. oC / %

MWHC

DT50 /DT90

(d)

(under

study

conditions)

DT50

(20°C,

pF2)

Fo

rm

.

fra

c.

χ2 Method

of

calculat

ion

Hoefchen am

Hohenseh – silt loam

– phenyl label

6.7 20°C/ 54%

of MWHC

48/159 48 0.6

9

4.3 SFO


EFSA Journal 2012;10(8):2860 40

Laacherhof, AXXa –

sandy loam – phenyl

label

6.4 20°C/ 54%

of MWHC

40/133 40 0.6

5

2.6 SFO

Laacherhof,

Wurmwiese –loam –

phenyl label

5.4 20°C/ 54%

of MWHC

40/133 40 0.6

2

6.4 SFO

Laacherhof, AIIIa –


6.6 20°C/ 54%

of MWHC

51/169 51 0.6

6

3.3 SFO

Springfield, Nebraska

- silt loam -phenyl

label

6.5 25°C/ 75%

1/3 bar

163/541 181 0.5

2

4.6 SFO

Springfield, Nebraska

- silt loam - pyrazole

label

6.5 25°C/ 75%

1/3 bar

191/634 212 0.5

6

9.7 SFO

Porterville, California

– sandy loam -

phenyl label

7.7 25°C/ 75%

1/3 bar

428 /1421 314 0.3

0

SFO

Porterville, California

– sandy loam -

pyrazole label

7.7 25°C/ 75%

1/3 bar

330 /1096 242 0.3

4

SFO

Geometric mean proposed by Applicant

(n=5)

59/196 60 0.

63

- -

Geometric mean proposed by RMS (n=6) 80/266 77 0.

58

- -

M02 metabolite Aerobic conditions (modelling endpoints

only for M02)

Soil type pH

(CaCl2)

t. oC /

%

MWHC

DT50

/DT90

(under

study

conditions)

DT50

(20°C,

pF2)

χ2 Method of

calculation

Hoefchen am Hohenseh – silt


6.7 20°C/

54% of

MWHC

115/382 115 4.3 SFO

Laacherhof, AXXa – sandy loam

– phenyl label

6.4 20°C/

54% of

MWHC

254/843 254 2.6 SFO

Hanscheider Hof – loam – phenyl

label

5.4 20°C/

54% of

MWHC

228/757 228 6.4 SFO

Dolendorf II – loam – phenyl

label

7.2 20°C/

54% of

MWHC

128/425 128 3.3 SFO

Springfield, Nebraska - silt loam

-phenyl label

6.5 25°C/

75%

1/3 bar

115/382 127 4.6 SFO


EFSA Journal 2012;10(8):2860 41

Springfield, Nebraska - silt loam

- pyrazole label

6.5 25°C/

75%

1/3 bar

133/442 147 9.7 SFO

Porterville, California – sandy

loam - phenyl label

7.7 25°C/

75%

1/3 bar

† † SFO

Porterville, California – sandy

loam - pyrazole label

7.7 25°C/

75%

1/3 bar

† † SFO

Geometric mean 160/532 164 - - † M02 only occurred at a single time point during the study and as such a kinetic consideration of this

metabolite is not possible.

‡ Data for M02 in EU soils from application to soil of M02. Springfield data derived from application of

parent to soil and this formation from parent and from M01 metabolite (ff 0.08 from parent and ff of 1 from

M01 – see Table B.8.31)


EFSA Journal 2012;10(8):2860 42

Field studies ‡

Penflufen Aerobic conditions

Location and Trial No. pH

(CaCl2

)

DT50 /DT90

(field days)

χ2 DT50

(20°C, pF2)

χ2 Method of

calculation

Vatteville, France,

R2006 0846/2

7.2/7.3

*

263/874 12.5 129 11.6 SFO

Great Chishill, UK,

R2006 0847/0

7.2/7.5

*

209/695 24.7 104 24.4 SFO

Igeloesa, Sweden,

R2006 0848/9

6.8/7.0

*

65/>1000c 8.5 224

a 8.9 DFOP

Burscheid, Germany,

R2006 0849/7

6.0/6.0

*

263 14.0 126 13.3 SFO

Albaro, Italy,

R2006 0850/0

7.4/7.5

*

-

71/770d

-

20.6

82 20.7 SFO

DFOP

Vilobi d‟Onyar, France,

R2006 0851/9

5.3/5.5

*

-

72/331e

-

7.4

68 10.7 SFO

DFOP

Geometric mean (n=6) 113b

* Depth (cm range) of pH determination 0-30/30-50 abased on the slow phase of the DFOP kinetics (k1 = 0.1007 d

-1 p=0.0245; k2 = 0.0031 d

-1 p = 0.0037; g = 0.46)

bsince the geomean of 113 d includes conservative DT50 of 224 d from the DFOP fit for Igeloesa it represents a

worst case for parent, but may underpredict formation of metabolites. The RMS derived an additional

alternative geomean DT50 of 63 d using the fast phase rate constant for the Igeloesa site and used this to examine

the impact on metabolite exposure values in the groundwater exposure assessment. c DFOP kinetics (k1 = 0.0373 d

-1 p=0.0119; k2 = 0.0012 d

-1 p = 0.0071; g = 0.5079, p=<0.0001)

d DFOP kinetics (k1 = 0.0207 d

-1 p=0.1325; k2 = 0.0019 d

-1 p = 0.1522; g = 0.5840, p=0.0294)

e DFOP kinetics (k1 = 0.3078 d

-1 p=0.1688; k2 = 0.0062 d

-1 p = <0.0001; g = 0.2155, p=<0.0001)

Soil adsorption/desorption (Annex IIA, point 7.1.2)

Parent ‡

Soil Type OC % Soil pH Kd

(mL/g)

Koc

(/g)

Kf

(mL/g)

Kfoc

(mL/g)

1/n

sandy loam („Laacher hof‟) 1.7 6.1 - - 4.929 289.9 0.8945

silt loam („Hoefchen‟) 2.3 6.3 - - 4.822 209.6 0.9077

Loam („Laacher hof‟) 1.2 5.3 - - 2.705 225.4 0.9736

loamy sand („Pikeville‟) 1.3 5.2 - - 5.323 409.5 0.9483

clay loam („Stanley‟) 2.3 5.9 - - 6.099 265.2 0.8749

Arithmetic mean 4.776 279.9 0.9198

pH dependence, Yes or No No

M01 metabolite

Soil Type OC % Soil

pH

Kd

(mL/g)

Koc

(/g)

Kf

(mL/g)

Kfoc

(mL/g)

1/n



Loam („Laacher hof‟) 1.9 5.1 - - 0.638 33.6 0.9497



Arithmetic mean 0.789 40.8 0.9337


EFSA Journal 2012;10(8):2860 43

pH dependence (yes or no) No

M02 metabolite

Soil Type OC % Soil

pH

Kd

(mL/g)

Koc

(/g)

Kf

(mL/g)

Kfoc

(mL/g)

1/n



Sandy loam („Laacher hof‟) 1.8 7.2 - - 19.059 1058.8 0.7900



Arithmetic mean 39.222 2011.8 0.7719

pH dependence (yes or no) No

N.B. excluding the results of the „Stanley‟ soil gave an arithmetic mean Kfoc of 1006 mL/g

and 1/n of 0.747 which were both used in the exposure assessment.

Mobility in soil (Annex IIA, point 7.1.3, Annex IIIA, point 9.1.2)

Column leaching ‡ No data were submitted nor required

Aged residues leaching ‡ No data were submitted nor required

Lysimeter/ field leaching studies ‡ No data were submitted nor required


EFSA Journal 2012;10(8):2860 44

PEC (soil) (Annex IIIA, point 9.1.3)

Parent (seasonal PECsoil)

Method of calculation

DT50 (d): 263 days (field, worst-case, best-fit, non-

normalised)


normalised)

Kinetics: SFO

Field or Lab: representative worst case from field studies

(Vatteville, France).

Parent (accumulative PECsoil)



normalised)

DT90 (d): >1000 days (field, worst-case, best-fit, non-

normalised)

Kinetics: DFOP

K1: 0.0373 day-1

K2: 0.0012 day-1

g: 0.5079

Field or Lab: representative worst case from field studies

(Igeloesa, Sweden).

Application data Crop: potato (tuber treatment and in furrow application)

Depth of soil layer: 5 cm.

Soil bulk density: 1.5 g/cm3

% plant interception: tuber treatment or in-furrow

application at planting therefore no crop interception

Number of applications: 1

Interval (d): bi-annual application

Application rate(s): 1 x 100 g as/ha

PEC(s)

(mg/kg)

Single

application

[100 g/ha]

Actual

Single

application

[100 g/ha]

Time weighted

average

Initial 0.133

Short term

24h

0.133 0.133

2d 0.133 0.133

4d 0.132 0.133

Long term 7d

7d

0.131 0.132

28d 0.124 0.129

50d 0.117 0.125

100d 0.102 0.117

Plateau concentration Peak concentration [100 g/ha]: 0.145 mg/kg after 24 yr

Steady state concentration [100 g/ha]: 0.012 mg/kg after 24 yr

(20 cm mixing depth calculated with MS Excel assuming

DFOP kimetics for the Igeloesa trial).

M01 metabolite


Molecular weight relative to the parent: 1.0504

(333.4/317.4)


EFSA Journal 2012;10(8):2860 45

DT50 (d): 394 days †

Kinetics: SFO

Field or Lab: Springfield, Nebraska

representative worst case from laboratory

studies.

Application data Application rate assumed: 16.6g as/ha seasonal

(22.6g as/ha for accumulation*)

(assuming M01 is formed at a maximum of

15.8% of the applied dose)‡

Crop interception: tuber treatment or in furrow

application at planting therefore no crop

interception

PEC(s)

(mg/kg)

Single

application

Actual

Single

application

Time weighted

average

Multiple

application

Actual

Multiple

application

Time weighted

average

Initial 0.022 -

Short term

24h

0.022 0.022 - -

2d 0.022 0.022 - -

4d 0.022 0.022 - -

Long term 7d

7d

0.022 0.022 - -

21d 0.021 0.022 - -

28d 0.021 0.022 - -

50d 0.020 0.021 - -

100d 0.019 0.020 - -

Plateau concentration Peak concentration 0.033 mg/kg (corrected for

molecular mass and maximum occurrence and occurs

8 years after parent has reached steady state).* † 394 day DT50 trigger value arises because best-fit for parent was based on FOMC kinetics and the lab

study was conducted at 25°C. The Geomean for the metabolite was 245d (314 d and 191 d for the two

labels) and corrected to 20°C using the Q10 of 2.58.

‡ Peak occurrence for the metabolite at the Springfield site was a mean of 15.8% for both the 273 and

365 d sampling intervals between the phenyl and the pyrazole labelled studies. Correction for the

relative molecular mass of parent and penflufen-3-hydroxy-butyl gives an assumed rate of 15.8 x

1.0504 = 16.6.

* Plateau concentration reached after 8 years, but parent takes 22 years. To calculate the peak steady

state for M01 after parent has reached steady state , we need to start the accumulation calculation after

22 years. To do this the steady state concentration of parent (0.012mg/kg) was converted to an

application rate over 20cm soil depth (0.012 x 3000), which gives 36 g parent/ha. Applying the same

assumptions for the extra parent applied changes the assumed application rate from 16.6g/ha to 16.6

g/ha + (36 x .166) = 22.576 g/ha. The steady state calculated over 5cm was 0.012 mg/kg and initial

peak concentration was 0.03 mg/kg. Converting the steady state to 20cm (0.012/4) and adding the

initial „peak‟ concentration gives a maximum potential plateau of 0.033 mg/kg.


EFSA Journal 2012;10(8):2860 46

M02 metabolite


Molecular weight relative to the parent: 0.8674

(275.3/317.4)

DT50 (d): 259 days (note that this DT50 was

derived by the Applicant from the kinetic

evaluation reported in the original laboratory

rate of degradation study performed with the

metabolite. In a separate kinetic fitting report,

a slightly revised maximum DT50 of 254 d was

accepted. Due to the negligible difference

between values used, the RMS accepted the use

of the 259 d DT50 in this calculation.

Kinetics: SFO

Field or Lab: Springfield, Nebraska

representative worst case from laboratory

studies.

Application data Application rate assumed: 8.5g as/ha seasonal

(9.265g as/ha for accumulation*)

(assuming M02 is formed at a maximum of

9.8% of the applied dose)‡

Crop interception: tuber treatment or in furrow

application at planting therefore no crop

interception

PEC(s)

(mg/kg)

Single

application

Actual

Single

application

Time weighted

average

Multiple

application

Actual

Multiple

application

Time weighted

average

Initial 0.011 x

Short term 1d

24h 0.011 0.011

x x

2d 0.011 0.011 x x

4d 0.011 0.011 x x

Long term 7d

7d 0.011 0.011

x x

21d 0.011 0.011

28d 0.011 0.011 x x

50d 0.010 0.011 x x

100d 0.009 0.010 x x

Plateau concentration Peak concentration 0.0125 mg/kg

(following 13 years accumulation of

parent and correction for molecular

mass and maximum occurrence). ‡ Peak occurrence for the metabolite at the Springfield site was the mean of 9.8% for the 273 d sampling

interval between the phenyl and the pyrazole labelled studies. Correction for the relative molecular

mass of parent and M02 gives an assumed rate of 9.8 x 0.8674 = 8.5g/ha.

* Plateau concentration reached after 2 years, but parent takes 22 years and M01 takes a further 8 years.

To calculate the peak steady state for M02 we need to start the accumulation calculation after the M01

has reached steady state. To do this the steady state concentration of the M01 metabolite (0.003mg/kg)

was converted to an application rate over 20cm soil depth (0.003 x 3000), which gives 9 g of the

precursor of M02 metabolite /ha. Applying the same assumptions for the extra „source‟ or the M02

metabolite applied changes the assumed application rate from 8.5g/ha to 8.5 g/ha + (9 x .0.085) =

9.265 g/ha. The steady state calculated over 5cm was 0.002 mg/kg and initial peak concentration was


EFSA Journal 2012;10(8):2860 47

0.012 mg/kg. Converting the steady state to 20cm (0.002/4) and adding the initial „peak‟ concentration

gives a maximum potential plateau of 0.0125 mg/kg.

Route and rate of degradation in water (Annex IIA, point 7.2.1)

Hydrolytic degradation of the active

substance and metabolites > 10 % ‡

pH 4: Hydrolytically stable at 50 C. (>99%

remaining after 7 days.

No further testing performed.

No major metabolites

pH 7: Hydrolytically stable at 50 C. (>99%




pH 9: Hydrolytically stable at 50 C. (97.5%




Photolytic degradation of active substance

and metabolites above 10 % ‡

Direct photolysis DT50 : 17.3 experimental days

Natural light, 130.6 days (Greece), 163.6 days

(London).

Indirect photolysis DT50: 3.98 experimental

days

Natural light, 33.1 days (Greece), 41.4 days

(London).

Photometabolite I 5-fluoro-1,3-dimethyl-1H-

pyrazole-4-carboxamide (M58) 6.8% AR (70 h

but still increasing)

Photometabolite II 5-fluoro-1,3 dimethyl-1H-

pyrazole-4-carboxylic acid 9.7% AR (70 h but

still increasing)

Quantum yield of direct

phototransformation in water at > 290

nm

3.74 x 10-4

Readily biodegradable ‡

(yes/no)

No data submitted, substance considered not

ready biodegradable.

Degradation in water / sediment

Penflufen Distribution (e.g. max in water x after n d. Max. sed x % after n d) † phenyl label/pyrazole label respectively

Water /

sediment

system

pH

water

phase

pH

sed

t. oC DT50-

DT90

whole

%

χ2

degDT50

-DT90

water

%

χ2

degDT

50-

DT90

%

χ2

Method of

calculation


EFSA Journal 2012;10(8):2860 48

sys. sed

Anglerweiher 7.4 7.0 19.9

±

0.3

170/18

3† –

564/60

8†

3.7/3.

5†

102/121† –

339/402†

3.7/4.9†

>1000 - SFO

Hoenniger

Weiher

6.8 5.2 19.9

±

0.3

295/25

9† –

979/86

0†

2.3/2.

0†

54/44† –

179/146†

7.4/11.

8†

>1000 - SFO

Geometric mean/median 221/73

4

74/246 >1000

Mineralisation and non extractable residues

Water /

sediment

system

pH

water

phase

pH

sed

Mineralisation

%AR after end of the study.

Non-extractable residues in

sed. % AR after end of the

study.

Anglerweiher 7.4 7.0 3.2% after 120 days (Ph)

0.8% after 120 days (Py)

12.2% after 120 days (Ph)


Hoenniger

Weiher

6.8 5.2 1.1% after 120 days (Ph)


17.6% after 120 days (Ph)

19.8% % after 120 days (Py)


EFSA Journal 2012;10(8):2860 49

PEC (surface water) and PEC sediment (Annex IIIA, point 9.2.3)

Penflufen

Parameters used in FOCUSsw step 1 and 2 Molecular weight (g/mol): 317.41

Water solubility (mg/L): 12.4 (20°C)

KOC (L/kg): 279.9

DT50 soil (d): 113 days (geometric field. In

accordance with FOCUS SFO)

DT50 water/sediment system (d):

(representative worst case from sediment water

studies)

DT50 water (d): 74 days geometric mean

DT50 sediment (d): 1000 d (default)

CAM value: „8 – incorp soil at one depth‟

DEPI: 5cm

Parameters used in FOCUSsw step 3 (if

performed)

Vapour pressure: 4.1 x 10-7

Pa

Koc (L/kg): 279.9

1/n: 0.9198

Plant uptake factor: 0

Application rate Crop: potato

Crop interception: 0

Number of applications: 1

Application rate(s): 100 g as/ha

Application window: March to May (Step 2)

Step 3 application date (window)

D3:5th

May (26 April-26 May)

D4:17th

May (08 May – 07 June)

D6:2nd

April (27 March – 26 April) 1st

cropping; 25th

July (22nd

July – 21st May) 2

nd

cropping

R1:26th

April (21 April – 21 May)

R2:1st March (01 March – 31 March)

R3: 28th

March (27 March – 26 April)

Main routes of entry 10 % runoff/drainage (at FOCUSsw Step 1); 2

% in Northern and 4 % in Southern Europe (at

Step 2 March-May)

FOCUS

STEP 1

Scenario

Day after

overall

maximum

PECSW (µg/L) PECSED (µg/kg)

Actual TWA Actual TWA

0 h 24.27 67.94

FOCUS STEP

2

Scenario

Day after

overall

maximum



Southern EU 0 h 9.4743 26.5187

24 h 9.3860 9.4302 26.5003 26.5095

2 d 9.3205 9.3917 26.3154 26.4587

4 d 9.1909 9.3237 25.9494 26.2954

7 d 8.9998 9.2257 25.4100 26.0312


EFSA Journal 2012;10(8):2860 50

FOCUS STEP

2

Scenario

Day after

overall

maximum



14 d 8.5694 9.0043 24.1946 25.4143

21 d 8.1595 8.7904 23.0373 24.8133

28 d 7.7692 8.5835 21.9353 24.2305

42 d 7.0437 8.1892 19.8871 23.1185

50 d 6.6600 7.9749 18.8037 22.5140

100 d 4.6927 6.7970 13.2493 19.1894

Values for Step 2, North Europe: PECsw; max = 4.737 µg/l, PECsed, max = 13.26µg/l

FOCUS

STEP 3

Scenario

Water

body

Day after

overall

maximum


Actual Actual

D3 Ditch 0 0.002 0.025

D4 Pond 0 0.081 0.480

D4 Stream 0 0.111 0.206

D6 Ditch 0 0.006 0.010

D6 Ditch 0 0.014 0.022

R1 Pond 0 < 0.001 < 0.001

R1 Stream 0 < 0.001 < 0.001

R2 Stream 0 < 0.001 < 0.001

R3 Stream 0 < 0.001 < 0.001

M01 metabolite


Water solubility (mg/L):95

KOC (L/kg): 41

DT50 soil (d): 60 days (Geomean, Lab. In

accordance with FOCUS SFO) †

DT50 water (d):1000 days

DT50 sediment (d):1000 days

Maximum occurrence in soil: 15.8%

Maximum occurrence in water: 12.8%


performed) Vapour pressure: 1.3 x 10

-9 (25°C, EPI Suite)

Koc: 41 ml/g

1/n: 0.934

† A soil DT50 of 77 days was accepted for the PECgw calculations and would be more appropriate for

future FOCUSsw calculations. However, it was not considered necessary to recalculate PECsw for this

metabolite as large margins of safety were calculated at STEP1.

FOCUS

STEP 1

Scenario

Day after

overall

maximum



0 h 5.25 2.15


EFSA Journal 2012;10(8):2860 51

FOCUS STEP

2

Scenario

Day after

overall

maximum



Southern EU 0 h 2.0034 0.8214

24 h 2.0020 2.0027 0.8208 0.8211

2 d 2.0006 2.0020 0.8202 0.8208

4 d 1.9978 2.0006 0.8191 0.8202

7 d 1.9937 1.9985 0.8174 0.8192

14 d 1.9840 1.9937 0.8134 0.8174

21 d 1.9744 1.9888 0.8095 0.8154

28 d 1.9648 1.9840 0.8056 0.8135

42 d 1.9459 1.9745 0.7978 0.8095

50 d 1.9351 1.9690 0.7934 0.8073

100 d 1.8692 1.9355 0.7664 0.7936 Values for Step 2, North Europe: PECsw; max = 1.002µg/l, PECsed, max = 0.411µg/l

M02 metabolite


Water solubility (mg/L): 3.6

KOC(L/kg): 1006 (worst case than calculated

geomean was used for the modelling)

DT50 soil (d): 164 days (Geomean, In

accordance with FOCUS SFO)

DT50 water (d): 1000 days

DT50 sediment (d): 1000 days

Maximum occurrence in soil: 9.8%

Maximum occurrence in water: Not observed


performed) Vapour pressure: 2.3 x 10

-6 (25°C, EPI Suite)

Koc (L/kg):1006

1/n:0.747

FOCUS

STEP 1

Scenario

Day after

overall

maximum



0 h 1.21 12.17

FOCUS STEP

2

Scenario

Day after

overall

maximum



Southern EU 0 h 0.4759 4.7875

24 h 0.4756 0.4757 4.7842 4.7859

2 d 0.4752 0.4756 4.7809 4.7842

4 d 0.4746 0.4752 4.7743 4.7809

7 d 0.4736 0.4747 4.7644 4.7759

14 d 0.4713 0.4736 4.7413 4.7644

21 d 0.4690 0.4725 4.7183 4.7529

28 d 0.4668 0.4713 4.6955 4.7414

42 d 0.4622 0.4690 4.6502 4.7185


EFSA Journal 2012;10(8):2860 52

FOCUS STEP

2

Scenario

Day after

overall

maximum



50 d 0.4597 0.4677 4.6244 4.7055

100 d 0.4440 0.4598 4.4669 4.6254 Values for Step 2, North Europe: PECsw; max = 0.238 µg/l, PECsed, max = 2.394µg/l

5-fluoro-1,3 dimethyl-1H-pyrazole-4-carboxylic acid metabolite

Parameters used in FOCUSsw step 3 Molecular weight (g/mol): 158.13

KOC(L/kg): 10.1 (EPISuite)

DT50 water (d): 1000 days (default)

DT50 sediment (d): 1000 days (default)

Maximum occurrence in soil: Not observed


FOCUS

STEP 3 SW

Scenario

PECsw, max

for

Penflufen

Averaged

monthly

hydraulic

residence

time

Potential

relevance of

metabolite

formation

in water

PECsw,

max

for

fluoro acid

penflufen

Date Value

(μg/L) (Days) (μg/L)

D3 ditch Feb. 6, 1993 0.002 1.0 No -

D4 pond Jan 29, 1986 0.081 103 Yes 0.005

D4 stream Dec. 9, 1985 0.111 <1 No -

D6 ditch* Nov. 5, 1986 0.006 7.6 No -

D6 ditch** Nov. 5, 1986 0.014 7.6 No -

R1 pond Mar 1, 1984 <0.001 156 Yes n.c.

R1 stream Mar 1, 1984 <0.001 <1 No -

R2 stream Mar 1, 1977 <0.001 <1 No -

R3 stream Mar 1, 1980 <0.001 <1 No - * = first season; ** = second season; n.c. = not calculated

Penflufen-pyrazole-4-carboxamide (M58)

metabolite

Parameters used in FOCUSsw step 1 and 2

Molecular weight (g/mol): 157.15

KOC(L/kg): 10.6 (EPISuite)

DT50 water (d): 1000 days (default)

DT50 sediment (d): 1000 days (default)

Maximum occurrence in soil: Not observed


FOCUS

STEP 3 SW

Scenario

PECsw, max

for

Penflufen

Averaged

monthly

hydraulic

residence

time

Potential

relevance of

metabolite

formation

in water

PECsw,

max

for

pyrazole-4-

carboxamid

e penflufen

Date Value

(μg/L) (Days) (μg/L)

D3 ditch Feb. 6, 1993 0.002 1.0 No -


EFSA Journal 2012;10(8):2860 53

D4 pond Jan 29, 1986 0.081 103 Yes 0.004

D4 stream Dec. 9, 1985 0.111 <1 No -

D6 ditch* Nov. 5, 1986 0.006 7.6 No -

D6 ditch** Nov. 5, 1986 0.014 7.6 No -

R1 pond Mar 1, 1984 <0.001 156 Yes n.c.

R1 stream Mar 1, 1984 <0.001 <1 No -

R2 stream Mar 1, 1977 <0.001 <1 No -

R3 stream Mar 1, 1980 <0.001 <1 No -

* = first season; ** = second season; n.c. = not calculated

PEC (ground water) (Annex IIIA, point 9.2.1) Method of calculation and type of study (e.g.

modelling, field leaching, lysimeter ) For FOCUS gw modelling, values used –

Modelling using FOCUS model(s), with

appropriate FOCUSgw scenarios, according to

FOCUS guidance.

Model(s) used: FOCUS PEARL 3.3.3

Scenarios (list of names): Châteaudun,

Hamburg, Jokioinen, Kremsmünster,

Okehampton,

Piacenza, Porto, Sevilla, Thiva

Crop: potato

Geometric mean DT50field Penflufen: 113 days

(applicant approach), 63 days (RMS approach

for metabolite assessment) (normalisation to

pF2, 20 C with Q10 of 2.58).

M01 metabolite DT50: 77 days (Geomean,

normalised, RMS adaptation).

M02 metabolite DT50: 164 days (Geomean,

normalised)

KOC: parent : 279.9 ml/g. 1/n= 0.9198

KOC: M01: 41 ml/g. 1/n= 0.934

KOC: M02: 1006 ml/g. 1/n= 0.747

Plant uptake factor: 0 for penflufen; 0.78 for

M01 metabolite; 0.75 for M02 metabolite

Application rate Application rate: 100 g/ha.

No. of applications:1 every 3 years

Time of application: 14 days before emergence


EFSA Journal 2012;10(8):2860 54

PEC(gw) - FOCUS modelling results (80th

percentile annual average concentration at 1m) using

parent DT50 of 113 days PE

AR

L /p

otato

Scenario penflufen

(µg/L)

Metabolite (µg/L)

M01 M02

Châteaudun 0.039 0.798 0.016

Hamburg 0.046 1.026 0.054

Jokioinen 0.005 0.675 0.008

Kremsmünster 0.041 0.705 0.016

Okehampton 0.048 0.844 0.023

Piacenza 0.151 0.825 0.041

Porto < 0.001 0.095 < 0.001

Sevilla < 0.001 0.275 0.003

Thiva 0.020 0.444 0.011

PEC(gw) - FOCUS modelling results (80

th percentile annual average concentration at 1m) using

parent DT50 of 63 days for potential increased metabolite formation PE

AR

L /p

otato

Scenario penflufen

(µg/L)

Metabolite (µg/L)

M01 M02

Châteaudun 0.001 1.123 0.018

Hamburg 0.019 1.417 0.058

Jokioinen <0.001 0.988 0.009

Kremsmünster 0.0016 1.058 0.017

Okehampton 0.0020 1.114 0.024

Piacenza 0.017 1.093 0.042

Porto < 0.001 0.515 0.001

Sevilla < 0.001 0.395 0.004

Thiva < 0.001 0.761 0.013

PEC(gw) From lysimeter / field studies No data submitted or required

Fate and behaviour in air (Annex IIA, point 7.2.2, Annex III, point 9.3)

Direct photolysis in air ‡ Not studied - no data requested Quantum yield of direct phototransformation Not studied - no data requested Photochemical oxidative degradation in air ‡ DT50 of 0.19 d derived by the Atkinson model

(version 1.91) based on a 12 hour OH radical

concentration assumed = 1.5 x 106 radical/cm

3

Volatilisation ‡ No data, volatilisation is considered unlikely

based on the physical chemical properties and

the representative use pattern Metabolites None

PEC (air)


Expert judgement, based on vapour pressure,

dimensionless Henry's Law Constant and

information on volatilisation from plants and

soil.

PECair


EFSA Journal 2012;10(8):2860 55

Maximum concentration

Expected to be negligible

Residues requiring further assessment

Environmental occurring metabolite requiring

further assessment by other disciplines (toxicology

and ecotoxicology).

Soil: penflufen, M01, M02

Surface Water: penflufen, M01, M02, M58, 5-

fluoro-1,3 dimethyl-1H-

pyrazole-4-carboxylic acid

Sediment: penflufen

Ground water: penflufen, M01, M02

Air: penflufen

Monitoring data, if available (Annex IIA, point 7.4)

Soil (indicate location and type of study) No data provided – none requested Surface water (indicate location and type of study)

No data provided – none requested

Ground water (indicate location and type of study)


Air (indicate location and type of study)


Points pertinent to the classification and proposed labelling with regard to fate and behaviour

data

Not readily biodegradable. Candidate for R53


EFSA Journal 2012;10(8):2860 56

Effects on terrestrial vertebrates (Annex IIA, point 8.1, Annex IIIA, points 10.1 and 10.3)

Species Test substance Time scale End point

(mg/kg bw per

day)

End point

(mg/kg

feed)

Birds

Bobwhite quail

(Colinus virginianus)

Technical

penflufen

Acute LD50 >4000 -

Bobwhite quail


Technical

penflufen Short-term LDD50 >1697 LC50 >8944

Mallard duck (Anas

platyrhynchos)

Technical

penflufen Short-term LDD50 >2208 LC50 >9923

Bobwhite quail


Technical

penflufen Long-term NOEL 96 NOEC 946

Mallard duck (Anas

platyrhynchos)

Technical

penflufen Long-term No regulatory endpoint

(NOEC/ NOAEC) can be

established due to likely

treatment related adverse

effects at the lowest tested

concentration.

Mammals

Rat Technical

penflufen

Acute LD50 >2000 -

Rat „Penflufen FS

050‟

Acute LD50 >2000 -

Rat Technical

penflufen

Long-term

(2-

generation

repro. study)

NOAEL 58

(males)

NOAEL 71

(females)

NOAEC

1000

Additional higher tier studies

The applicant has referred to a German field study which includes an assessment of

the occurrence, abundance and foraging behaviour of birds and mammals in potato

fields. The results of the study are not considered to be critical to the penflufen risk

assessment, but do indicate that birds and mammals may feed in potato fields –

confirming the need for a terrestrial vertebrate risk assessment. LDD = lethal dietary dose


EFSA Journal 2012;10(8):2860 57

Toxicity/exposure ratios for terrestrial vertebrates (Annex IIIA, points 10.1 and 10.3)

Crop and application rate: Potato tuber seed treatment at 20 mg penflufen/kg tubers (equivalent to 100

g a.s./ha at an assumed maximum tuber planting rate of 5 tonnes/ha)

Indicator species/Category² Time

scale

ETE (mg

a.s. /kg bw

per day)

TER Annex VI

Trigger

Tier 1 (Birds)

Medium herbivore Acute 1.52 >2632 10

Small insectivore Acute 2.08 >1923 10

Medium herbivore Short-term 1.52 >1116 10

Small insectivore Short-term 2.08 >816 10

Medium herbivore Long-

term*

5

Small insectivore Long-

term*

5

Common crane (Grus grus)

– risk from consumption of

treated potato tubers as sole

diet (i.e. PD & PT = 1)

Acute 8.8 >455 10

Short-term 8.8 >193 10

Long-

term*

5

Earthworm-eating birds Long-

term*

5

Fish-eating birds Long-

term*

5

Tier 1 (Mammals)

Medium herbivore Acute 0.56 >3571 10

Small insectivore Acute 1.26 >1587 10

Medium herbivore Long-term 0.56 104 5

Small insectivore Long-term 1.26 46 5

Wild boar (Sus scrofa) – risk

from consumption of treated

potato tubers as sole diet (i.e.

PD & PT = 1)

Acute 4.0 >500 10

Long-term 4.0 14.5 5

Earthworm-eating mammals Long-term 0.75394 77 5

Fish-eating mammals Long-term 0.002049 28306 5


EFSA Journal 2012;10(8):2860 58

* No risk assessments could be done since no regulatory endpoint (NOEC/ NOAEC) could be

established

Toxicity data for aquatic species (most sensitive species of each group) (Annex IIA, point 8.2,

Annex IIIA, point 10.2)

Group Test substance Time-scale

(Test type)

End point Toxicity1

(mg/L)

Laboratory tests ‡

Fish

Carp (Cyprinus carpio) Penflufen

(technical)

Acute,

96h, static LC50 0.103 (mm)

Carp (Cyprinus carpio) Penflufen

FS 050

Acute,

96h, static LC50

1.68 product (nom)

0.083 penflufen

(nom)

Fathead minnow

(Pimephales promelas)

Penflufen

(technical)

Chronic, 35d,

flow-through

(ELS)

NOEC 0.0234 (mm)

Carp (Cyprinus carpio) M01 Acute,

96h, static LC50 >15.7 (mm)

Carp (Cyprinus carpio) M02 Acute,

96h, static LC50 >0.799 (mm)

Aquatic invertebrate

Water flea

(Daphnia magna)

Penflufen

(technical)

Acute, 48h,

static

EC50

(immobilisation) >4.66 (mm)

Water flea

(Daphnia magna)

Penflufen

FS 050

Acute, 48h,

static

EC50

(immobilisation)

85.0 product (nom)

4.19 penflufen

(nom)

Water flea

(Daphnia magna)

Penflufen

(technical)

Chronic, 21d,

static-renewal NOEC 1.53 (mm)

Oyster

(Crassostrea virginica,

marine species)

Penflufen

(technical)

Acute, 96h,

flow-through

EC50 (inhibition

of shell

deposition)

1.3 (mm)

Daphnia magna M01 Acute, 48h,

static

EC50


Daphnia magna M02 Acute, 48h,

static

EC50


Sediment dwelling organisms

Chironomid midge

(Chironomus dilutus,

formerly C. tentans)

Penflufen

(technical)

Acute, 10day,

spiked

sediment (2nd

to 3rd

instar

larvae).

LC50

>8.28 mg a.s./L

pore water (mm)

(>63.8 mg a.s./kg

dw sediment) (mm)


EFSA Journal 2012;10(8):2860 59

Group Test substance Time-scale

(Test type)

End point Toxicity1

(mg/L)

Algae

Pseudokirchneriella

subcapitata

Penflufen

(technical)

Growth

inhibition, 72

and 96h,

static

72h EbC50

72h ErC50

>5.1 (mm)

>5.1 (mm)

Pseudokirchneriella

subcapitata

Penflufen

FS 050

Growth

inhibition, 96

72h, static

72h EbC50

72h ErC50

>100 product

>4.93 a.s. (nom)

>100 product

>4.93 a.s. (nom)

Pseudokirchneriella

subcapitata M01

Growth

inhibition,

72h, static

72h EbC50

72h ErC50

66.5 (nom)

>75.0 (nom)

Pseudokirchneriella

subcapitata M02

Growth

inhibition,

72h, static

72h EbC50

72h ErC50

>1.0 (nom)

>1.0 (nom)

Higher plant

Lemna gibba Penflufen

(technical)

Growth

inhibition, 7d,

static renewal

7 day EbC50

7 day EyC50

>4.7

>4.7

Microcosm or mesocosm tests: Not submitted and not required. 1 Based on nominal (nom) or mean measured concentrations (mm).


EFSA Journal 2012;10(8):2860 60

Toxicity/exposure ratios for the most sensitive aquatic organisms (Annex IIIA, point 10.2)

FOCUS Step1

Crop and application rate: Potato tuber seed treatment at 20 mg penflufen /kg tubers (equivalent to

100g a.s./ha at an assumed maximum tuber planting rate of 5 tonnes /ha)

Test

substance

Organism Time scale

& endpoint

measured

Toxicity

end point

value

(µg a.s. or

metabolite

/l)

Step 1

PECMAX.

(µg a.s. or

metabolite

/l)

TER # Annex

VI

Trigger

Penflufen

(technical) Carp (Cyprinus

carpio)

Acute

96h LC50

103 24.27 4.2 100

Fathead minnow

(Pimephales

promelas)

Chronic

(ELS) 35day

NOEC

23.4 24.27 1.0 10

Water flea

(Daphnia magna)

Acute

48h EC50

>4660

24.27 >192 100

Water flea

(Daphnia magna)

Chronic

21day

NOEC

1530 24.27 63 10

Saltwater oyster

(Crassostrea

virginica)

Acute 96h

EC50 (shell

growth)

1300 24.27 54 100

Algae (Pseudo-

kirchneriella

subcapitata)

Growth

inhibn.72h

Eb/ErC50

>5100 24.27 >210 10

Higher aquatic

plants (Lemna

gibba)

Growth

inhibn. 7day

Eb /ErC50

>4700 24.27 >194 10

M01 Carp

(Cyprinus carpio)

Acute

96h LC50

>15700 5.25 >2990 100

Water flea

(Daphnia magna)

Acute

48h EC50

>62000 5.25 >11809 100

Algae (Pseudo-

kirchneriella

subcapitata)

Growth

inhibition

72h EbC50

>66500 5.25 >12667 10

M02 Carp

(Cyprinus carpio)

Acute

96h LC50

>799 1.21 >660 100

Water flea

(Daphnia magna)

Acute

48h EC50

>3120 1.21 >2578 100

Algae (Pseudo-

kirchneriella

subcapitata)

Growth

inhibn. 72h

Er/EyC50

>1000 1.21 >826 10

# TERs in breach of Annex VI triggers are included in bold


EFSA Journal 2012;10(8):2860 61

FOCUS Step 2


100g a.s./ha at an assumed maximum tuber planting rate of 5 tonnes /ha)

TERs cover both Northern and Southern Europe Member States –being calculated using the highest

maximum PECsw

Test

substance

Organism

Time scale

& endpoint

measured

Toxicity

end point

value

(µg a.s. or

metabolite

/l)

Step 2

PECMAX.

(µg a.s. or

metabolite

/l)

TER # Annex

VI

Trigger

Penflufen


carpio)

Acute:

96h LC50

103 9.474 10.9 100

Fathead minnow

(Pimephales

promelas)

Chronic

(ELS) 35day

NOEC

23.4 9.474 2.5 10

Saltwater oyster

(Crassostrea

virginica)

Acute: 96h

EC50 (shell

growth)

1300 9.474 137 100

# TERs in breach of Annex VI triggers are included in bold

Refined aquatic risk assessment using higher tier FOCUS modelling.

FOCUS Step 3


100g a.s. /ha at an assumed maximum tuber planting rate of 5 tonnes /ha)

TERs cover both Northern and Southern Europe Member States –being calculated using the highest

maximum PECsw

Test

substance

Organism Time scale &

endpoint

measured

Toxicity

end point

value

(µg a.s. /l)

Step 3

PECMAX.

(µg a.s. /l)

TER Annex

VI

Trigger

Penflufen


carpio)

Acute:

96h LC50

103 0.111 928 100

Fathead minnow

(Pimephales

promelas)

Chronic,

35day,

flow-through

(ELS)

23.4 0.111 211 10

Bioconcentration

Penflufen Penflufen-3-

hydroxy

butyl‟

Penflufen-

pyrazolyl-

AAP‟

Log PO/W 3.3 1.7 2.1


EFSA Journal 2012;10(8):2860 62

Bioconcentration

Bioconcentration factor

(BCF)

142 (based on total 14

C)

16 (based on

measured a.s.)

- -

Annex VI Trigger for the

bioconcentration factor

3.0 3.0 3.0

t(1/2) for clearance (maximum

value in days) (whole fish

CT50)

0.53 - -

Time to reach 95% clearance

(maximum value in days)

(whole fish CT95)

2.28 - -

Level and nature of residues

(%) in organisms after the 14

day depuration phase

98% depuration of 14

C radio-activity

after 14 days

- -

Effects on honeybees (Annex IIA, point 8.3.1, Annex IIIA, point 10.4)

Test substance Acute oral toxicity

(LD50 µg/bee)

Acute contact

toxicity (LD50

µg/bee)

Penflufen (technical) >108.2 µg a.s./bee >100 µg a.s./bee

„Penflufen FS 050‟ >105.3 µg a.s./bee >100 µg a.s./bee

Field or semi-field tests: None submitted and not required.

Hazard quotients for honey bees (Annex IIIA, point 10.4)

Not calculated since the use of HQs is only appropriate for the risk assessment of spray

treatments and not for the proposed potato tuber seed treatment use. The exposure to bees

from the on-planter spraying is considered negligible.

Risk Assessment for bees

Crop and application rate: Potato tuber seed treatment at 20 mg penflufen /kg tubers

(equivalent to 100g a.s. /ha at an assumed maximum tuber planting rate of 5 tonnes /ha)

The main potential route of exposure of a forager bee is considered to be from foraging on

flowers with contaminated nectar. A risk assessment for foraging bees based on recently

published guidance (ref. OEPP/EPPO Bulletin 40, 1-9, 2010) had been conducted. This

assessment is considered to be sufficient to also cover the risk to bees foraging on

contaminated aphid honey dew.

Potential residue in nectar = 0.002 µg a.s. /mg (extrapolation from the residue data on potato

leaves)

Ingestion rate = 128 mg sugar equates with 256 mg nectar assuming 50% sugar content of the

nectar

ETE = 256 x 0.002 = 0.512 µg penflufen per bee per day

Bee acute oral TER = 105.3/0.512= 206

Effects on other arthropod species (Annex IIA, point 8.3.2, Annex IIIA, point 10.5)

Laboratory tests with standard sensitive species


EFSA Journal 2012;10(8):2860 63

Species Test

Substance

End point Effect

(LR50 g/ha)

Typhlodromus pyri „Penflufen FS

050‟

Mortality (glass

plate residual

toxicity study)

>250 g a.s. /ha

Aphidius rhopalosiphi „Penflufen FS

050‟

Mortality (glass

plate residual

toxicity study)

>250 g a.s. /ha

No other terrestrial arthropod studies were reported.

Terrestrial non-target arthropod risk assessment

Crop and application rate: Potato tuber seed treatment at 20 mg penflufen /kg tubers

(equivalent to 100g a.s. /ha at an assumed maximum tuber planting rate of 5 tonnes /ha)

The ESCORT2 Hazard Quotient approach is not appropriate for seed treatment formulations.

Penflufen exposure to crop-dwelling and ground-dwelling non-target arthropods from the

proposed potato tuber seed treatment use is likely considered to be low. This low level of

exposure, combined with the reported low toxicity of penflufen to non-target arthropods

reported in the „first tier‟ ESCORT2 studies and also in other toxicity studies with soil-

dwelling arthropods, is considered sufficient to indicate a low risk to non-target arthropods.


EFSA Journal 2012;10(8):2860 64

Effects on earthworms, other soil macro-organisms and soil micro-organisms (Annex IIA points

8.4 and 8.5. Annex IIIA, points, 10.6 and 10.7)

Test organism Test substance Time scale End point1

Earthworms

Eisenia fetida Penflufen

(technical)

Acute 14 days LC50 =

>1000 mg technical a.s. /kg

dw soil

Corrected LC50 =

>500 mg technical a.s. /kg

dw soil

Eisenia fetida „Penflufen FS 050‟ Chronic 8

weeks

NOEC =

33 mg a.s. /kg dw soil ##

(670 mg product /kg dw

soil)

Corrected NOEC =

16.5 mg a.s. /kg dw soil ##


soil)

Eisenia fetida M01 Chronic 8

weeks

NOEC =

1000 mg met. /kg dw soil


weeks

NOEC =


Corrected NOEC =


Other soil macro-organisms

Hypoaspis aculeifer

(soil mite)

„Penflufen FS 050‟ Chronic 14

days

NOEC =

493 mg a.s. /kg dw soil


soil)

Corrected NOEC =

246.5 mg a.s. /kg dw soil


soil)

Hypoaspis aculeifer

(soil mite)

M01 Chronic 14

days

NOEC =


Hypoaspis aculeifer

(soil mite)

M02 Chronic 14

days

NOEC =


Corrected NOEC =



EFSA Journal 2012;10(8):2860 65


Folsomia candida

(collembola)

„Penflufen FS 050‟ Chronic 28

days

NOEC =

231 mg a.s. /kg dw soil


soil)

Corrected NOEC =

115.55 mg a.s. /kg dw soil


soil)

Folsomia candida

(collembola)

M01 Chronic 28

days

NOEC =


Folsomia candida

(collembola)

M02 Chronic 28

days

NOEC =


Corrected NOEC =


Soil micro-organisms

Nitrogen

mineralisation

Penflufen

(technical)

28 days < 25% effects at 3.18 mg

pure a.s. (3.33mg technical)

/kg dw soil

Nitrogen

mineralisation

„Penflufen FS 050‟ 28 days < 25% effects at 3.33 mg

pure a.s. (65.6 µL product)

/kg dw soil #

Nitrogen

mineralisation

M01 28 days < 25% effects at 3.51 mg

metabolite /kg dw soil

Nitrogen

mineralisation



Carbon

mineralisation

Penflufen

(technical)

28 days < 25% effects at 3.18 mg

pure a.s. (3.33mg technical)

/kg dw soil

Carbon

mineralisation

„Penflufen FS 050‟ 28 days < 25% effects at 3.33 mg

pure a.s. (65.6 µL product)

/kg dw soil #

Carbon

mineralisation



Carbon

mineralisation



Field studies


EFSA Journal 2012;10(8):2860 66


The results of a scientifically valid „litter bag‟ organic matter breakdown study indicates a

lack of ecologically significant adverse effects on organic matter decomposition some 12

months after initial exposure - based on <10% differences from the untreated control (i.e.

breakdown in untreated plots of 88% compared with 82% in treated plots). Treated plots

included a soil incorporated concentration of 250 µg a.s./kg dw soil plus an „annual

application rate‟ of 100 g a.s./ha. Soil incorporated concentrations were in excess of the

maximum accumulated peak soil PEC from the proposed use of 145 µg a.s. /kg dw soil. 1 The EPPO correction factor of 2 has been applied to the laboratory toxicity endpoints (where log

Pow >2), irrespective of whether the artificial test soil contains 10% or 5% organic matter

# Endpoint units converted from uL product /kg dw soil based on an analysed concentration of 50.78 g

penflufen /litre product

## Endpoint units converted from grams product /kg dw soil based on an analysed concentration of

4.93% w/w penflufen (50.78g a.s./L)

Toxicity/exposure ratios for soil organisms

Crop and application rate

Test organism Test substance Time scale Soil

PEC1

TER Trigger

Earthworms

Eisenia fetida Penflufen

(technical)

Acute 14 days 0.145

mg a.s.

/kg dw

soil

>3448 10

Eisenia fetida „Penflufen FS

050‟

Chronic 8

weeks

0.145

mg a.s.

/kg dw

soil

114 5


weeks

0.033

mg met.

/kg dw

soil

30303 5


weeks

0.0125

mg met.

/kg dw

soil

20000 5

Other soil macro-organisms

Hypoaspis

aculeifer (soil

mite)

„Penflufen FS

050‟

Chronic 14

days

0.145

mg a.s.

/kg dw

soil

1700 5

Hypoaspis

aculeifer (soil

mite)

M01 Chronic 14

days

0.033

mg met.

/kg dw

soil

30303 5

Hypoaspis

aculeifer (soil

mite)

M02 Chronic 14

days

0.0125

mg met.

/kg dw

soil

40000 5


EFSA Journal 2012;10(8):2860 67

Test organism Test substance Time scale Soil

PEC1

TER Trigger

Folsomia candida

(collembola)

„Penflufen FS

050‟

Chronic 28

days

0.145

mg a.s.

/kg dw

soil

797 5

Folsomia candida

(collembola)

M01 Chronic 28

days

0.033

mg met.

/kg dw

soil

30303 5

Folsomia candida

(collembola)

M02 Chronic 28

days

0.0125

mg met.

/kg dw

soil

40000 5

1 Refers to maximum accumulated peak PEC soil

Effects on non-target plants (Annex IIA, point 8.6, Annex IIIA, point 10.8)

Preliminary screening data:

No data available.

Laboratory dose response tests

No reliable data available.

Non-target plant risk assessment

Based on a lack of significant exposure from the proposed potato seed treatment use, the risk

to non-target plants situated in adjacent off-field areas is considered to be low.

Effects on biological methods for sewage treatment (Annex IIA 8.7)

Test type/organism End point

Activated sludge EC50 (respiration) = > 1000 mg technical

penflufen /litre (nominal)

Ecotoxicologically relevant compounds (consider parent and all relevant metabolites requiring

further assessment from the fate section)

Compartment Ecotoxicologically relevant compounds

soil penflufen

water penflufen

sediment penflufen

groundwater penflufen


EFSA Journal 2012;10(8):2860 68

Classification and proposed labelling with regard to ecotoxicological data (Annex IIA, point 10

and Annex IIIA, point 12.3)

RMS/peer review proposal

Active substance R50, R53, S60, S61.


EFSA Journal 2012;10(8):2860 69

APPENDIX B – USED COMPOUND CODE(S)

Code/Trivial name* Chemical name** Structural formula**

M01 (penflufen-3-

hydroxy-butyl)

5-fluoro-N-[2-(3-hydroxy-1,3-

dimethylbutyl)phenyl]-1,3-

dimethyl-1H-pyrazole-4-

carboxamide (IUPAC)

NHN

N

O

F

CH3

CH3

CH3

CH3

CH3

OH

M02 (penflufen-

pyrazolyl-AAP)

N-(2-acetylphenyl)-5-fluoro-1,3-

dimethyl-1H-pyrazole-4-

carboxamide (IUPAC) NHN

N

O

OF

CH3

CH3

CH3

M49 (penflufen-

homoglutathione)

gamma-glutamyl-S-(4-{[2-(1,3-

dimethylbutyl)phenyl]carbamoyl}-

1,3-dimethyl-1H-pyrazole-5-

yl)cysteinyl-beta-alanine

NH

NH

OO

NHN

N

O

S

CH3

CH3

CH3

CH3

CH3

O

OH

NH2

O

OH

M58 (penflufen-

pyrazole-4-

carboxamide)

5-fluoro-1,3-dimethyl-1H-

pyrazole-4-carboxamide

N

N

O

F

CH3

CH3

NH2

M61 (penflufen-

desmethyl-4-

carboxylic acid)

5-fluoro-3-methyl-1H-pyrazole-4-

carboxylic acid

M63 (penflufen-

desmethyl-

dicarboxylic acid)

5-fluoro-1H-pyrazole-3,4-

dicarboxylic acid

N

NH

O

F

OH

OOH

OHN

NH

O

F

CH3


EFSA Journal 2012;10(8):2860 70

M64 (penflufen-bis-

desmethyl-3-

carboxylic acid)

5-fluoro-1H-pyrazole-3-carboxylic

acid

N

NH F

OOH

M65 (penflufen-bis-

desmethyl-3-

carbonyl-serine)

structure not completely specified,

one possible isomer is shown

N

NH F

Oserine

NH

O

OH

OH

NH

NF

O

conjugation at 3-carbonyl, possible isomer

5-fluoro-1,3 dimethyl-

1H-pyrazole-4-

carboxylic acid

5-fluoro-1,3 dimethyl-1H-

pyrazole-4-carboxylic acid

HN

N

F

O

OH


EFSA Journal 2012;10(8):2860 71

ABBREVIATIONS

1/n slope of Freundlich isotherm

λ wavelength

decadic molar extinction coefficient

°C degree Celsius (centigrade)

µg microgram

µm micrometer (micron)

a.s. active substance

AChE acetylcholinesterase

ADE actual dermal exposure

ADI acceptable daily intake

AF assessment factor

AOEL acceptable operator exposure level

AP alkaline phosphatase

AR applied radioactivity

ARfD acute reference dose

AST aspartate aminotransferase (SGOT)

AV avoidance factor

BCF bioconcentration factor

BUN blood urea nitrogen

bw body weight

CAS Chemical Abstracts Service

CFU colony forming units

ChE cholinesterase

CI confidence interval

CIPAC Collaborative International Pesticides Analytical Council Limited

CL confidence limits

cm centimetre

d day

DAA days after application

DAR draft assessment report

DAT days after treatment

DFOP double first-order in parallel

DM dry matter

DT50 period required for 50 percent disappearance (define method of estimation)

DT90 period required for 90 percent disappearance (define method of estimation)

dw dry weight

EbC50 effective concentration (biomass)

EC50 effective concentration

ECHA European Chemical Agency

EEC European Economic Community

EINECS European Inventory of Existing Commercial Chemical Substances

ELINCS European List of New Chemical Substances

EMDI estimated maximum daily intake

ER50 emergence rate/effective rate, median

ErC50 effective concentration (growth rate)

EU European Union

EUROPOEM European Predictive Operator Exposure Model

f(twa) time weighted average factor

FAO Food and Agriculture Organisation of the United Nations

FIR Food intake rate

FOB functional observation battery

FOCUS Forum for the Co-ordination of Pesticide Fate Models and their Use

FOMC first-order multi-compartment kinetics


EFSA Journal 2012;10(8):2860 72

FS flowable concentrate for seed treatment

g gram

GAP good agricultural practice

GC gas chromatography

GCPF Global Crop Protection Federation (formerly known as GIFAP)

GGT gamma glutamyl transferase

GHS Globally Harmonized System of Classification and Labelling of Chemicals

GM geometric mean

GS growth stage

GSH glutathion

h hour(s)

ha hectare

Hb haemoglobin

Hct haematocrit

hL hectolitre

HPLC high pressure liquid chromatography

or high performance liquid chromatography

HPLC-MS high pressure liquid chromatography – mass spectrometry

HQ hazard quotient

IEDI international estimated daily intake

IESTI international estimated short-term intake

ILV inter laboratory validation

ISO International Organisation for Standardisation

IUPAC International Union of Pure and Applied Chemistry

JMPR Joint Meeting on the FAO Panel of Experts on Pesticide Residues in Food and

the Environment and the WHO Expert Group on Pesticide Residues (Joint

Meeting on Pesticide Residues)

Kdoc organic carbon linear adsorption coefficient

kg kilogram

KFoc Freundlich organic carbon adsorption coefficient

L litre

LC liquid chromatography

LC50 lethal concentration, median

LC-MS liquid chromatography-mass spectrometry

LC-MS/MS liquid chromatography with tandem mass spectrometry

LD50 lethal dose, median; dosis letalis media

LDD lethal dietary dose

LDH lactate dehydrogenase

LOAEL lowest observable adverse effect level

LOD limit of detection

LOQ limit of quantification (determination)

m metre

M/L mixing and loading

MAF multiple application factor

MCH mean corpuscular haemoglobin

MCHC mean corpuscular haemoglobin concentration

MCV mean corpuscular volume

mg milligram

mL millilitre

mm millimetre

mN milli-newton

MRL maximum residue limit or level

MS mass spectrometry

MSDS material safety data sheet

MTD maximum tolerated dose


EFSA Journal 2012;10(8):2860 73

MWHC maximum water holding capacity

NESTI national estimated short-term intake

ng nanogram

NOAEC no observed adverse effect concentration

NOAEL no observed adverse effect level

NOEC no observed effect concentration

NOEL no observed effect level

OECD Organisation for Economic Co-operation and Development

OM organic matter content

Pa pascal

PBI plant back interval

PD proportion of different food types

PEC predicted environmental concentration

PECair predicted environmental concentration in air

PECgw predicted environmental concentration in ground water

PECsed predicted environmental concentration in sediment

PECsoil predicted environmental concentration in soil

PECsw predicted environmental concentration in surface water

pH pH-value

PHED pesticide handler's exposure data

PHI pre-harvest interval

PIE potential inhalation exposure

pKa negative logarithm (to the base 10) of the dissociation constant

Pow partition coefficient between n-octanol and water

PPE personal protective equipment

ppm parts per million (10-6

)

ppp plant protection product

PT proportion of diet obtained in the treated area

PTT partial thromboplastin time

QSAR quantitative structure-activity relationship

r2 coefficient of determination

REACH Registration, Evaluation, Authorisation of CHemicals

RPE respiratory protective equipment

RUD residue per unit dose

SC suspension concentrate

SD standard deviation

SFO single first-order

SSD species sensitivity distribution

STMR supervised trials median residue

t1/2 half-life (define method of estimation)

TER toxicity exposure ratio

TERA toxicity exposure ratio for acute exposure

TERLT toxicity exposure ratio following chronic exposure

TERST toxicity exposure ratio following repeated exposure

TK technical concentrate

TLV threshold limit value

TMDI theoretical maximum daily intake

TRR total radioactive residue

TSH thyroid stimulating hormone (thyrotropin)

TWA time weighted average

UDS unscheduled DNA synthesis

UV ultraviolet

W/S water/sediment

w/v weight per volume

w/w weight per weight


EFSA Journal 2012;10(8):2860 74

WBC white blood cell

WG water dispersible granule

WHO World Health Organisation

wk week

yr year

efsa report

Documents

european commission

dossier peer

pesticide risk assessment

summary penflufen

regulatory risk assessment

new active substance

key words penflufen

competent authority